TOPICS

Selected Abstracts from Maui Derm 2022 for Dermatologists

J Clin Aesthet Dermatol. 2022;15(4 Suppl 1):S8–S35.


A message from the Guest Editor and Maui Derm Program Director, George Martin, MD

Click the cover to access the digital version of this supplement.

Dear colleagues:

The 2022 edition of the Maui Derm for Dermatologists meeting had a variety of clinical and scientific data presented, but not just at the podium. A wide range of clinically relevant material was also presented in poster format. For those of you who were unable to participate in the meeting or were not able to attend the poster sessions, we have compiled abstracts from a select group of research posters presented during the 2022 meeting. It is my hope that you will find the highlighted research informative and thought provoking.

With aloha,

George Martin, MD

MauiDerm 2022 Program Director; Guest Editor, The Journal of Clinical and Aesthetic Dermatology


Funding for this supplement was provided by Amgen.

CONTENT

ACNE

  • A new frontier in acne treatment: Encapsulated benzoyl peroxide and tretinoin
  • Efficacy and safety of narrow-spectrum oral sarecycline for moderate to severe facial and truncal acne vulgaris
  •  Management of truncal acne with oral sarecycline: Pooled results from two Phase 3 clinical trials

 

ACTINIC KERATOSIS

  • Tirbanibulin ointment 1% for actinic keratosis: Pooled data from two Phase 3 studies

 

AESTHETIC DERMATOLOGY

  • Subject-relevant outcomes of on-label 50U abobotulinumtoxin A treatment for moderate to severe glabellar lines across three individual trials

 

ATOPIC DERMATITIS

  • A randomized, double-blind, vehicle-controlled Phase 2a study evaluating once-daily roflumilast foam 0.3% in patients with moderate to severe seborrheic dermatitis
  • Effects of ruxolitinib cream on pruritus and sleep in atopic dermatitis: 52-week pooled results from two Phase 3 studies
  • Efficacy and safety of dupilumab in children aged ≥6 months to <6 years with moderate to severe atopic dermatitis
  • Efficacy and safety of tralokinumab in adolescents with moderate to severe atopic dermatitis: Results of the Phase 3 ECZTRA 6 trial
  • Long-term efficacy of baricitinib 2mg for the treatment of atopic dermatitis in North America
  • Interim analysis results from a proof-of-concept study for ASLAN004 in adult moderate to severe atopic dermatitis: A double blind, randomized, placebo-controlled study
  • Long-term safety data for dupilumab up to four years in an open-label extension study of adults with moderate to severe atopic dermatitis
  • Mechanism and proof of concept for a novel, orally delivered, gut-restricted drug candidate for the treatment of atopic dermatitis and other inflammatory diseases
  • Oral difelikefalin reduces pruritus in atopic dermatitis
  • Tapinarof cream 1% once daily for the treatment of moderate to severe atopic dermatitis in children and adults: The pivotal Phase 3 ADORING clinical program
  • Two-year maintenance of response with tralokinumab in moderate to severe atopic dermatitis: Interim analysis of the ECZTEND open-label extension trial

 

CUTANEOUS ONCOLOGY

  • Adjuvant pembrolizumab versus placebo in high-risk locally advanced cutaneous squamous cell carcinoma: The Phase 3 KEYNOTE-630 study
  • Appropriate utilization of the prognostic 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma (cSCC) demonstrated by clinical reports and physician evaluation of real-world cases
  • A comprehensive diagnostic offering workflow increases the rate of actionable results of the 23- and 35-gene expression profile tests for use as ancillary diagnostic tools for difficult-to-diagnose melanocytic lesions
  • Evidence review of the prognostic 40-gene expression profile test for cutaneous squamous cell carcinoma
  • Integrating the 31-gene expression profile and clinicopathologic data to determine the disk of sentinel lymph node positivity and distant metastasis-free survival in cutaneous melanoma
  • PLATforM: Descriptive analysis from a randomized, Phase 2 study of novel spartalizumab combinations in previously treated unresectable/metastatic melanoma
  • Tumor burden in patients with locally advanced basal cell carcinoma and metastatic basal cell carcinoma following treatment with sonidegib: Results of the 42-month BOLT study

 

HAIR

  • Clinical efficacy of the oral JAK3/TEC inhibitor ritlecitinib (PF-06651600) and patients’ perception of improvement in alopecia areata: results from the ALLEGRO Phase 2b/III trial
  • Long-term efficacy of a nutraceutical supplement for promoting hair growth in perimenopausal, menopausal and postmenopausal women with self-perceived thinning hair

 

MISCELLANEOUS

  • Overview of ongoing and upcoming clinical trials in autoimmune blistering diseases: pemphigus vulgaris and pemphigus foliaceus (ADDRESS and ADDRESS+) and bullous pemphigoid

 

PRURITUS

  • A Phase 2b/III, randomized, placebo-controlled, two-arm trial evaluating oral nalbuphine extended release for pruritus relief in prurigo nodularis: The PRISM study protocol

 

PSORIASIS

  • A pooled analysis of randomized, controlled, Phase 3 trials investigating the efficacy and safety of a novel, fixed-dose calcipotriol and betamethasone dipropionate cream for the topical treatment of plaque psoriasis
  • Bimekizumab efficacy and safety up to two years in patients with moderate to severe plaque psoriasis switching from ustekinumab: results from the interim BE BRIGHT open-label extension trial
  • Bimekizumab versus secukinumab in plaque psoriasis: higher efficacy translates into benefits in patient-perceived symptoms and health-related quality of life in the BE RADIANT multicenter, randomized, double-blinded Phase 3b trial
  • Certolizumab pegol three-year durability of efficacy for moderate to severe plaque psoriasis in different subgroups: CIMPASI-1 and CIMPASI-2
  • Combined analysis of two head-to-head Phase 3 trials demonstrating superior improvement of patient reported outcomes for calcipotriene and betamethasone dipropionate cream compared to gel/topical suspension in treatment of plaque psoriasis
  • Comparative effectiveness of guselkumab in psoriatic arthritis: Updates to a systematic literature review and network meta-analysis
  • Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, compared with placebo and apremilast in moderate to severe plaque psoriasis: Integrated laboratory parameter results from the Phase 3 POETYK PSO-1 and PSO-2 Trials
  • Differences in patient and dermatologist perspectives on psoriasis treatment: Results from the UPLIFT survey
  • Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPSaKE 1
  • Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPSaKE 2
  • Efficacy of certolizumab pegol in psoriasis patients failing to respond to etanercept: Three‑year results from the randomized Phase 3 CIMPACT trial 
  • Efficacy of Spesolimab for the rapid control of generalized pustular psoriasis flares: results from the placebo-controlled Effisayil™ 1 study
  • Improvement in psoriasis symptoms and involvement in special areas: 32-week results from ADVANCE
  • Maintenance of absolute Psoriasis Area and Severity Index (PASI) responses with guselkumab through five years (Week 252) among patients who achieved absolute PASI ≤2 at Week 16 in the VOYAGE 1 study
  • Mechanism and proof of concept for a novel, orally delivered, gut-restricted drug candidate for the treatment of psoriasis and other inflammatory diseases
  • Mind.Px—personalized medicine for psoriasis biologic treatment
  • Safety and efficacy of bimekizumab through two years in patients with moderate to severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the BE BRIGHT open-label extension trial
  • Safety and efficacy of once-daily roflumilast cream 0.3%, a potent phosphodiesterase-4 inhibitor, for the treatment of psoriasis in the DERMIS-1 and DERMIS-2 Phase 3 trials
  • Secukinumab dosing every two weeks versus every four weeks demonstrates superior efficacy in adult patients with plaque psoriasis weighing 90kg or more, and benefits PASI 90 non-responder patients who up-titrate at Week 16
  • Tapinarof cream 1% once daily for plaque psoriasis: Long-Term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent

 

ROSACEA

  • Encapsulated benzoyl peroxide (E-BPO): A novel formulation of BPO for long-term management of rosacea

 


ACNE


A new frontier in acne treatment: encapsulated benzoyl peroxide and tretinoin

Presenters: Del Rosso JQ,1 Sugarman J,2 Gold M,3,4 Arekapudi KL,5 Green LJ,6

Affiliations: 1JDR Research; 2University of California San Francisco; 3Gold Skin Care Center; 4Tennessee Clinical Research Center; 5Galderma Laboratories, L.P.; 6Dept of Dermatology, George Washington University School of Medicine

Background: Multiple studies demonstrate the efficacy of benzoyl peroxide (BPO) in combination with topical retinoids, such as tretinoin, in the treatment of acne vulgaris. However, BPO degrades tretinoin through a process of oxidative decomposition. Treatment with BPO and tretinoin can also result in significant skin irritation, and there is evidence suggesting that their irritative effects may be additive. Silica microencapsulation of both BPO and tretinoin enhances the stability of this combination by keeping BPO from degrading tretinoin and allowing a controlled release of both agents to the skin while decreasing irritation. Here, we report the efficacy and safety results from two Phase 3 studies of microencapsulated BPO/tretinoin (E-BPO/T), a fixed-dose combination of microencapsulated tretinoin 0.1% and BPO 3% cream.

Methods: 858 subjects nine years of age or older with moderate to severe acne were enrolled in two multicenter, double-blind, parallel-group, vehicle-controlled trials and randomized (2:1) to 12 weeks of once-daily E-BPO/T or vehicle cream. Co-primary endpoints were the proportion of subjects achieving greater than or equal to two grades reduction from baseline and Clear (Grade 0) or Almost Clear (Grade 1) at Week 12 on an Investigator Global Assessment (IGA); and absolute changes from baseline in inflammatory and non-inflammatory lesion counts baseline to Week 12. Safety and tolerability were assessed through cutaneous safety assessments, local tolerability assessments, adverse event (AE) reporting, physical examination, and vital signs.

Results: E-BPO/T was significantly superior to vehicle for all primary endpoints in both trials. In Study 1, 39.9% of subjects treated with E-BPO/T achieved IGA success versus 14.3% for vehicle. The respective values in Study 2 were 26.8 percent and 15.1% In Study 1, the changes from baseline in inflammatory lesion count for E-BPO/T were –21.6 vs –14.8 for vehicle (P<0.001), and in Study 2 were –16.2 vs –14.1 (P=0.018), respectively. In Study 1, the changes from baseline in non-inflammatory lesions for E-BPO/T were –29.7 versus –19.8 for vehicle (P<0.001), and in Study 2 were –24.2 and –17.4 (P<0.001). E-BPO/T was well tolerated in both studies. The most reported adverse reactions were application site pain (10.6%), dryness (4.9%), exfoliation (4.1%), and erythema (4.0%).

Conclusion: Treatment with E-BPO/T provided statistically significant improvements in IGA scores and reduced both inflammatory and non-inflammatory lesions in subjects with moderate to severe acne. The study met all primary endpoints and demonstrated significant improvement over vehicle at 12 weeks, with no treatment-related serious adverse events. E-BPO/T demonstrated good tolerability, with no clinically meaningful differences from vehicle at Week 12. E-BPO/T is shown to be an effective and safe fixed-dose regimen for treatment of moderate to severe acne.

Funding: Study funded by Sol-Gel Technologies Ltd.; poster support provided by Galderma Laboratories, L.P., Fort Worth, TX.

 

Efficacy and safety of narrow-spectrum oral sarecycline for moderate to severe facial and truncal acne vulgaris 

 Presenters: Moore AY,1,2 Green LJ,3 Johnson JL,4 Grada A5

Affiliations: 1Baylor University Medical Center, Dallas, Texas, 2Arlington Research Center, Arlington, Texas, 3Lawrence J. Green, MD, LLC, George Washington University School of Medicine, Washington, DC 4Departments of Dermatology and Pathology, Feinberg School of Medicine, Northwestern University, 5R&D and Medical Affairs, Almirall (US), Exton, Pennsylvania

Background: Sarecycline is a tetracycline-class antibiotic for the treatment of moderate to severe acne. Its narrow-spectrum antibacterial activity and lipophilicity may minimize side effects commonly associated with broad-spectrum tetracyclines, such as minocycline and doxycycline. Here, we report the results of two identically designed, Phase 3 pivotal trials, SC1401 and SC1402, to evaluate the efficacy and safety of once-daily sarecycline 1.5mg/kg for 12 weeks in patients aged 9 to 45 years with moderate to severe acne vulgaris on the face and trunk. 

Methods: Efficacy was assessed in a total of 2,002 subjects. Patients 9 to 45 years of age with moderate to severe facial acne (Investigator’s Global Assessment [IGA] score greater than or equal to three, 20–50 inflammatory and ≤ 100 non-inflammatory lesions, and ≤ 2 nodules) were randomized 1:1 to sarecycline 1.5 mg/kg/day or placebo for 12 weeks. Co-primary efficacy endpoints included reduction in inflammatory lesion count and IGA success, defined as IGA score of 0 (clear) or 1 (almost clear) and at least a two-point improvement from baseline at Week 12. Secondary endpoints included nonfacial IGA (chest and back).

Results: In SC1401 and SC1402, at Week 12, IGA success (≥2-grade improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P<0.0001 and P=0.0038). Onset of efficacy in inflammatory lesions occurred by Week 3, with mean percentage reduction at Week 12 in SC1401 and SC1402 of −52.2% and −50.8.% (sarecycline), respectively, versus −35.2% and −36.4% (placebo; P<0.0001). Onset of efficacy for absolute reduction of noninflammatory lesion count occurred at Week 6 in SC1401 (P<0.05) and Week 9 in SC1402 (P<0.01). Statistically significant improvement in truncal acne (back and chest) were reported in both trials. In SC1401, the most common treatment-emergent adverse events (TEAEs) (in ≥2% of either sarecycline or placebo group) were nausea (4.6% [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1%; 1.7%), headache (2.7%; 2.7%), and vomiting (2.1%; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in less than or equal to one percent of sarecycline patients. Among females, vulvovaginal candidiasis (SC1401: 1.1% [sarecycline] and 0 [placebo]); SC1402: (0.3% and 0) and mycotic infection (0.7% and 0; 1.0% and 0) rates were very low.

Conclusion: The FDA-approved narrow-spectrum antibiotic sarecycline was safe, well-tolerated, and effective for moderate to severe acne in patients nine years of age and older, with low incidence of side effects commonly associated with tetracycline antibiotics.

Funding: Financial support was provided by Almirall, LLC.

 

Management of truncal acne with oral sarecycline: pooled results from two Phase 3 clinical trials

Presenters: Del Rosso JQ,1 Gold LS,2 Baldwin H,3 Harper JC,4 Zeichner J,5 Obagi S,6 Graber E,7 Jimenez X,8 Vicente FH,9 Salem R,8 and Grada A10

Affiliations: 1JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 2Dermatology Clinical Research, Henry Ford Health System, Detroit, MI; 3Department of Dermatology, Acne Treatment & Research Center, Morristown, NJ; 4Dermatology and Skin Care Center of Birmingham, Birmingham, AL; 5Mount Sinai Hospital, New York, NY; 6Boston University School of Medicine; 7Dermatology Institute of Boston, Boston, MA; Northeastern University, Boston, MA; 8Medical Affairs, Almirall LLC., Exton, PA; 9Global Clinical Statistics, Almirall SA., Barcelona, Spain;10 R&D and Medical Affairs, Almirall LLC., Exton, PA 

Background: Acne vulgaris is a common skin disease that affects the face, chest, and back. While truncal acne is present in at least 50 percent of patients, clinical studies have focused predominantly on facial acne.1,2 Few treatments to date have been evaluated for truncal acne. Sarecycline is a narrow-spectrum, third-generation, tetracycline-class oral drug approved for the treatment of acne. Pivotal Phase 3 studies show that sarecycline is safe, well-tolerated, and effective treatment for moderate to severe acne vulgaris.

Methods: Pooled analysis was performed for truncal acne results with sarecycline from the two Phase 3 studies. Investigator Global Assessment (IGA) success was evaluated at Weeks 3, 6, 9, and 12.

Results: Chest IGA success rate were significantly greater with sarecycline versus placebo at Weeks 3 (11.84% vs. 7.71%, respectively; p=0.0192), 6 (18.81% vs. 14.03%, respectively; p=0.0390), and 12 (33.42% vs. 20.77%, respectively; p<0.0001). Back IGA success rate were also significantly greater with sarecycline versus placebo group at Weeks 3 (12.13% vs. 7.04%, respectively; p=0.0023), 6 (18.42% vs. 14.34%, respectively; p=0.0412), 9 (29.05% vs. 19.88%, respectively; p=0.0004) and 12 (33.07% vs. 21.91%, respectively; p<0.0001).

Conclusion: Sarecycline efficacy for truncal acne was observed within three weeks after treatment, supporting sarecycline as an optimal choice for oral treatment of moderate to severe truncal acne.

Funding: Financial support provided by Almirall, LLC.


ACTINIC KERATOSIS


Tirbanibulin ointment 1% for actinic keratosis: pooled data from two Phase 3 studies

Presenters: Blauvelt A,1 Kempers S,2 Schlesinger T,3 Lain E,4 Wang H,5 Cutler D,5 Lebwohl M6, Fang J,5 Kwan R5

Affiliations: 1Oregon Medical Research Center, Portland, OR; 2Minnesota Clinical Study Center, New Brighton, MN; 3Clinical Research Center of the Carolinas, Charleston, SC; 4Austin Institute for Clinical Research, Pflugerville, TX; 5Athenex, Inc., Buffalo, NY; 6Icahn School of Medicine at Mount Sinai, New York, NY.

Background: Tirbanibulin is a novel inhibitor of tubulin polymerization developed as a topical formulation for actinic keratosis (AK). We have previously shown that five days of tirbanibulin ointment is safe and superior to vehicle in AK clearance in two Phase 3 studies. Here, we present pooled data analyses on efficacy and safety with a one-year follow-up.

Methods: Two identical Phase 3 randomized, double-blinded, vehicle-controlled studies (KX01-AK-003/KX01-AK-004) evaluated efficacy and safety of tirbanibulin ointment 1% vs. vehicle in adults with AK on face/scalp. Eligible subjects with 4 to 8 clinically visible AK lesions in a 25-cm2 area were randomized 1:1 to receive tirbanibulin or vehicle (5-day once-daily self-application). Primary and secondary endpoints were complete (100%) and partial (≥75%) clearance of AK lesions at Day (D) 57. Safety including adverse events (AEs) and local skin reactions (LSRs, Grade 0 [none] – 3 [severe]) was assessed up to D57. Subjects with complete AK clearance at D57 were followed for one year to assess safety and clearance durability.

Results: Eligible subjects (predominantly Caucasian males, mean age of 70 years, Skin Type II, median of six AK lesions in the treatment area) were randomized to receive tirbanibulin (n=353) or vehicle ointment (n=349). At D57, complete clearance rates were significantly higher with tirbanibulin versus vehicle, 49% versus 9% (P<0.0001); partial clearance rates were 72%  versus 18%, respectively (P<0.0001). Median reduction in AK lesion count to D57 was greater with tirbanibulin versus vehicle (87.5% vs. 20%). Treatment-related AEs were few and mostly mild transient application-site pruritus (tirbanibulin vs. vehicle: 9% vs 6%) and pain (tirbanibulin vs vehicle: 10% vs 3%). LSR signs were present at baseline, increased after treatment, peaked at D8 and resolved by D29. Maximum mean±standard deviation composite LSR scores (grades sum of all 6 LSR categories, possible range: 0-18) were 4.1±2.32 and 1.0±1.14 for tirbanibulin and vehicle group, respectively. LSRs were mostly transient mild or moderate erythema and flaking/scaling; severe LSRs were few. All LSRs resolved, stabilized or returned to baseline and did not require intervention. No deaths, discontinuations, or serious AEs related to tirbanibulin occurred. At one-year post-D57 follow-up, Kaplan-Meier estimate of proportion of tirbanibulin-treated patients (n=174) with at least one lesion present at baseline in the treated area recurring during follow-up was 47% and estimated rate of subjects with any AK lesion (recurred or new) was 73 percent. No treatment-related AEs throughout one-year follow-up were reported.

Conclusion: Tirbanibulin ointment 1% applied for five days was well tolerated, safe and effective, potentially making it a valuable new addition to AK treatment.

Funding: Funding was provied Athenex, Inc.

Disclosures: AB has served as a scientific advisor and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma; SK receiving consulting fees from Foamix Pharmaceuticals and Kinex–Athenex and receiving grant support from and serving as an investigator for Arcutis Biotherapeutics (Trial of Roflumilast Cream for Chronic Plaque Psoriasis). TS has served as a consultant/speaker with honorarium, advisor and/or investigator for Almirall, Biofrontera, Galderma, Leo, Ortho and Sun Pharmaceuticals. EL has been a clinical investigator, consultant, advisor, and/or paid speaker for Almirall, Athenex, Gage Pharmaceuticals, UCB, Abbvie, Sanofi, Regeneron, Vyne Pharmaceuticals, Pfizer, Amgen, Novartis, Eli Lilly, Kadmon, Chemocentryx, Bausch Health, Galderma, Dermavant, Arcutis, Bristol Myers Squibb, Kiniksa, Mindera, Sebacia, Pulse BioSciences, Leo Pharmaceuticals, Aclaris, Biorasi, Brickell, Cassiopea, Dr Reddy, Endo Pharmaceuticals, and G&E Herbal Biotechnology. HW, DC, JF, and RK are employees of Athenex. ML has received research funds (paid to Institution) from: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Incyte, Janssen / Johnson & Johnson, Kadmon, Leo Pharmaceuticals, Medimmune/Astra Zeneca, Novartis, Pfizer, Sciderm, UCB, Ortho-dermatologics, and Vidac. He is also a consultant for Allergan, Aqua, Arcutis, Boehringer-Ingelheim, Bristol Myers Squibb, LEO Pharma, Menlo, Mitsubishi Pharma/Neuroderm LTD, Promius/Dr. Reddy, Regeneron, Theravance Biopharma, and Verrica.


AESTHETIC DERMATOLOGY


Subject-relevant outcomes of on-label 50U abobotulinumtoxin A treatment for moderate to severe glabellar lines across three individual trials

Presenters: Glaser DA,1 Cox SE,2 Amir Moradi A,3 Dayan S,4 Jacob C,5 Schlessinger J6 Joseph J,7 Bill Andriopoulos B8

Affiliations: 1Saint Louis University, St. Louis, MO; 2Aesthetic Solutions, Chapel Hill, NC; 3Moradi M.D., Vista, CA; 4DeNova Research, Chicago, IL; 5Chicago Cosmetic Surgery and Dermatology; Northwestern University’s Feinberg School of Medicine, Department of Dermatology, Chicago, IL; 6Skin Specialists, Omaha, NE; 7Clinical Testing of Beverly Hills, Encino, CA; 8Galderma Laboratories, L.P., Fort Worth, TX

Background: The 50U dose of abobotulinumtoxinA (ABO) is approved for glabellar line (GL) treatment. Here we present efficacy, subject satisfaction, and safety results from three recent clinical trials using this dose, with a focus on ≥1-grade glabellar line improvement and subject satisfaction, reflecting clinical outcomes of significance for the subjects. 

Methods: Subjects with moderate to severe GL were treated with 50U ABO and followed for 6 to 9 months in three studies (NCT03736928, double-blind, Phase 2; NCT03960957, double-blind, Phase 3; NCT03687736, open-label, Phase 4). Evaluations included investigator- and subject-assessed GL severity scale (GLSS), a subject satisfaction questionnaire, subject-reported onset of effect (diary), and adverse events. 

Results: In each study, 80, 224, and 120 subjects were evaluated, the majority achieving improvement in GLSS. Median time to onset of effect was two days in all three studies. At Month 6, 53%, 46% and 37% of subjects in each trial maintained ≥1-grade improvement in investigator-assessed GLSS, and at Month 9, 18% of subjects in the Phase 2 trial still had ≥1-grade improvement. The majority of subjects were satisfied with their treatment and found the result to be natural-looking up to Month 6 in all three trials. Treatment-related adverse events were mostly mild, and none were serious. 

Conclusion: ABO 50U for glabellar line treatment was efficacious and well-tolerated across all three trials, with rapid onset, and ≥1-grade improvement and subject satisfaction lasting for up to 6 to 9 months after injection.

Funding: Research funded by Galderma Research & Development, LLC.


ATOPIC DERMATITIS


A randomized, double-blind, vehicle-controlled Phase 2a study evaluating once daily roflumilast foam 0.3% in patients with moderate to severe seborrheic dermatitis

Presenters: Zirwas M,1 Draelos Z ,2 DuBois J,3 Kircik LH,4 Moore AY,5 Gold LS,6 Alonso-Llamazares J,7 Bukhalo M,8 Bruce S,9 Eads K,10 Green LJ,11 Guenthner ST,12 Ferris LK,13 Forman S,14 Kempers SE,15 Lain E,16 Lynde CW,17 Pariser D,18 Toth DP,19 Yamauchi PS20 Feng A21, Higham RC,21 Burnett P,21 Berk DR21.

Affiliations: 1Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH; 2Dermatology Consulting Services, High Point, NC; 3DermResearch, Inc., Austin, TX; 4Icahn School of Medicine at Mount Sinai, NY, Indiana Medical Center, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, and Skin Sciences, PLLC, Louisville, KY; 5Arlington Center for Dermatology, Arlington Research Center, Arlington, TX; Baylor University Medical Center, Dallas, TX; 6Henry Ford Medical Center, Detroit, MI; 7Driven Research LLC, Coral Gables, FL; 8Arlington Dermatology, Rolling Meadows, IL; 9SBA Dermatology, Houston, TX; 10The Indiana Clinical Trials Center, PC, Plainfield, IN; 11George Washington University School of Medicine, Rockville, MD; 12The Dermatology Center of Indiana, PC, Plainfield, IN; The Indiana Clinical Trials Center, PC, Plainfield, IN; 13University of Pittsburgh, Department of Dermatology, Pittsburgh, PA; 14ForCare Medical Center, Tampa, FL; 15Minnesota Clinical Study Center, Fridley, MN; 16Sanova Dermatology, Austin, TX; 17University of Toronto, Toronto, Lynde Centre for Dermatology, Markham, and Probity Medical Research, Markham, ON, Canada; 18Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA; 19XLR8 Medical Research, Probity Medical Research, Windsor, ON, Canada; 20David Geffen School of Medicine at UCLA, Los Angeles, and Dermatology Institute & Skin Care Center, Inc., Santa Monica, CA; 21Arcutis Biotherapeutics, Inc., Westlake Village, CA.

Background: Seborrheic dermatitis (SD) is a chronic, inflammatory condition with scaling, erythematous, hyperpigmented, or hypopigmented patches on the scalp, face, upper trunk, and intertriginous areas. Affected individuals may experience itching, stress, or low self-esteem and need effective, well-tolerated treatments that are safe for chronic use on scalp and non-scalp locations. Topical roflumilast is a selective, highly potent phosphodiesterase-4 inhibitor. Here, we report results from a Phase 2, eight-week, vehicle-controlled, double-blind study evaluating safety and efficacy of once-daily roflumilast foam 0.3% in patients with moderate or severe SD (NCT04091646). 

Objective: Here, we present results from a post-hoc analysis aiming to identify responders to baricitinib 2mg with a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement from the Phase 3 monotherapy trial BREEZE-AD5 (NCT03435081).

 Methods: Participants (≥18 years) with SD involving less than or equal to 20 percent body surface area (BSA; scalp and/or rest of body) and moderate or severe disease severity (Investigator Global Assessment [IGA] score 3−4) were randomized 2:1 to once-daily roflumilast 0.3% or vehicle foam (maximum application area ≤20% BSA) for eight weeks. 

Results: A total of 226 patients were randomized (roflumilast: n=154; vehicle: n=72). Baseline disease characteristics were comparable between groups. The primary efficacy endpoint, IGA Success (Clear/Almost Clear plus ≥2-grade improvement) at Week 8, was achieved by 73.8 percent and 40.9 percent of the roflumilast and vehicle foam groups, respectively (P<0.0001); 35.5 percent and 15.2 percent, respectively, were clear (IGA=0). Significant efficacy with roflumilast foam 0.3% was observed for numerous secondary endpoints, including IGA Success at Week 2 (33.8% vs 14.7%; P=0.0033) and Week 4 (56.6% vs 28.4%; P=0.0002); erythema success at Week 8 (44.7% vs 21.2%; P=0.0021); scaling success at Week 8 (56.0% vs 27.3%; P=0.0003); and, among patients with baseline Worst Itch Numeric Rating Scale (WI-NRS) ≥4 (n=184/226 [81.4%]), WI-NRS success (≥4-point improvement) at Week 2 (52.8% vs 23.2%; P=0.0007) and Week 8 (64.6% vs 34.0%; P=0.0007). The treatment benefit of roflumilast over vehicle was also supported by change from baseline in BSA at Week 8 (P<0.0001) and improvement in Dermatology Life Quality Index (P=0.0380 at Week 8). Excellent tolerability was observed for roflumilast foam 0.3% with greater than or equal to 98 percent of patients rated as having “no evidence of irritation” by the investigator. Overall incidence of treatment-emergent adverse events (TEAE) and TEAEs leading to discontinuation were low with similar rates between roflumilast and vehicle; no serious AEs were reported.

Conclusion: Once-daily roflumilast foam 0.3% significantly improved disease severity, erythema, scaling, quality of life, and itch with onset of action as early as Week 2 (first post-baseline visit). Roflumilast foam 0.3% was well-tolerated with low rates of AEs, supporting further study of roflumilast foam 0.3% as a promising treatment option for patients with moderate or severe SD.

Funding: Funding was provided by Arcutis Biotherapeutics, Inc.

Effects of ruxolitinib cream on pruritus and sleep in atopic dermatitis: 52-week pooled results from two Phase 3 studies

Presenters: Simpson E,1 Boguniewicz M,2 Thaçi, D,3 Misery L,4 Armstrong A,5 Silverberg JI,6 Venturanza ME,7 Kallender H,7 Gao J,7 Szepietowski JC,8

Affiliations: 1Oregon Health & Science University, Portland, OR; 2National Jewish Health, Denver, CO; 3University of Lübeck, Lübeck, Germany; 4University Hospital of Brest, Brest, France; 5University of Southern California, Los Angeles, CA; 6George Washington University, Washington, DC; 7Incyte Corporation, Wilmington, DE; 8Department of Dermatology, Venereology, and Allergology, Wroclaw Medical University, Wroclaw, Poland

Background: Atopic dermatitis (AD) is a highly pruritic, inflammatory skin disease. Quality of life can be significantly reduced by pruritus and sleep disturbances. Ruxolitinib cream is a topical formulation of ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor. 

Methods: In two Phase 3 AD studies of identical design (TRuE-AD1/TRuE-AD2), patients (≥12 years with AD for ≥2 years, Investigator’s Global Assessment score 2/3, 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib cream, or vehicle cream for an eight-week, double-blind, vehicle-controlled period (VC; continuous treatment). Patients subsequently continued in a double-blind long-term safety period (LTS; as-needed treatment) to Week 52. Patients initially randomized to ruxolitinib cream remained on their regimen during the LTS; patients on vehicle were rerandomized (1:1) to either ruxolitinib cream strength. During the LTS, patients treated areas with active AD only, stopped treatment three days after lesion clearance, and restarted treatment upon recurrence. Here, the effects of ruxolitinib cream on itch and sleep during the LTS are reported using pooled results from the two studies. Itch and sleep were assessed using questions 1 and 2 of the Patient-Oriented Eczema Measure (POEM Q1/Q2). Sleep-related impairment and sleep disturbance were also assessed using items 8a and 8b of the Patient-Reported Outcomes Measurement Information System (PROMIS).

Results: Of 1249 randomized patients, 1,072 (85.8%) continued into the LTS; 1,031 (median age, 33.0 years) were evaluated for efficacy (n=409/428/98/96 for 0.75% ruxolitinib cream/1.5% ruxolitinib cream/vehicle to 0.75% ruxolitinib cream/vehicle to 1.5% ruxolitinib cream). At Week 8, the proportions of patients reporting no days of itch per POEM Q1 were 27.7%/32.7%/9.2%/9.5% for 0.75% ruxolitinib cream/1.5% ruxolitinib cream/vehicle to 0.75% ruxolitinib cream/vehicle to 1.5% ruxolitinib cream, respectively. During as-needed application of ruxolitinib cream in the LTS, itch relief was maintained for patients who remained in the ruxolitinib cream (0.75%/1.5%) groups (Week 52: 28.0%/36.2%). In the vehicle to ruxolitinib cream (0.75%/1.5%) groups, more patients reported no days of itch at Week 52 (36.1%/43.2%) vs Week 8. The proportions of patients reporting no nights of disturbed sleep per POEM Q2 at Week 8 were 64.9%/71.8%/48.0%/41.1%. At Week 52, patients who remained in the ruxolitinib cream groups maintained undisturbed sleep (both 74.5%). More patients who switched from vehicle to ruxolitinib cream (0.75%/1.5%) reported no nights of disturbed sleep at Week 52 (73.6%/80.2%) vs Week 8. At baseline, PROMIS sleep-related impairment mean scores were 17.3/17.4/17.0/16.6. Scores decreased slightly in the ruxolitinib cream groups by the beginning of the LTS, indicating less impairment (15.2/15.2/16.0/16.7), and decreased slightly in all groups to Week 52 (14.4/14.4/14.8/13.8). PROMIS sleep disturbance mean scores at baseline were 18.9/19.2/18.2/18.9, decreased slightly in the ruxolitinib cream groups by the beginning of the LTS (17.4/17.4/18.8/19.6), and were maintained or slightly decreased to Week 52 (16.8/17.2/17.0/16.2).

Conclusion: In summary, itch and sleep were improved with ruxolitinib cream, and these improvements were maintained for 44 weeks with as-needed ruxolitinib cream use. Patients who switched from vehicle to ruxolitinib cream at Week 8 had similar itch and sleep scores at Week 52 to patients initially randomized to ruxolitinib cream.

Funding: This study was funded by Incyte Corporation (Wilmington, DE, USA). Writing assistance was provided by Vicky Kanta, PhD, an employee of ICON (North Wales, PA) and was funded by Incyte Corporation.

Disclosures: ELS is an investigator for AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron and is a consultant with honorarium for AbbVie, Eli Lilly, Forte Bio, Galderma, Incyte Corporation, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant. 

MB is an investigator for Incyte Corporation. DT has served as an investigator and/or consultant/advisor for AbbVie, Almirall, Amgen, Asana Biosciences, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Target-Solution, and UCB; and has received grants from AbbVie, Celgene, LEO Pharma, and Novartis. 

LM is an investigator for AbbVie, Eli Lilly, Galderma, Incyte Corporation, LEO Pharma, Pfizer, and Sanofi; and is a consultant with honorarium for AbbVie, Eli Lilly, Galderma, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, and Sanofi. AWA has served as a research investigator and/or scientific advisor to AbbVie, Bristol Myers Squibb, Dermavant, Dermira, Incyte Corporation, Janssen, LEO Pharma, Lilly, Modmed, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. 

JIS has received honoraria for advisory board, speaker, and consultant services from AbbVie, Asana BioSciences, Bluefin, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Incyte Corporation, Kiniksa, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Realm, Regeneron, and Sanofi; and research grants for investigator services from Galderma and GlaxoSmithKline. 

MEV, HK, and JG are employees and shareholders of Incyte Corporation. JCS has served as an advisor for AbbVie, LEO Pharma, Menlo Therapeutics, Novartis, Pierre Fabre, and Trevi; has received speaker honoraria from AbbVie, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Sanofi-Genzyme, and Sun Pharma; and has received clinical trial funding from AbbVie, Almirall, Amgen, Galapagos, Holm, Incyte Corporation, InflaRX, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB.

 

Efficacy and safety of dupilumab in children aged ≥ 6 months to < 6 years with moderate to severe atopic dermatitis

Presenters: Paller A,1,2 Siegfried EC,3,4 Simpson E,5 Wollenberg A,6 Gonzalez ME7, Sidbury R,8 Lockshin B,9 Sun Y,10 O’Malley JT,11 Bansal A10

Affiliations: 1Northwestern University Feinberg School of Medicine, Chicago, IL; 2Ann and Robert H. Lurie Children’s Hospital, Chicago, IL; 3Saint Louis University, St. Louis, MO; 4Cardinal Glennon Children’s Hospital, St. Louis, MO; 5Oregon Health and Science University, Portland, OR; 6Ludwig-Maximilian University, Munich, Germany; 7University of Miami Miller School of Medicine, Miami, FL ; 8Seattle Children’s Hospital, Seattle, WA; 9Georgetown University, Rockville, MD; 10Regeneron Pharmaceuticals, Inc., Tarrytown, NY; 11Sanofi, Cambridge, MA

Background: There is a high unmet medical need in pediatric patients aged six months to <6 years with moderate to severe atopic dermatitis (AD), with lack of approved systemic treatments. Previous studies showed that dupilumab substantially improved AD-associated signs, symptoms, and quality-of-life, with a favorable safety profile in adults, adolescents, and children aged ≥6 years. Here, we present pivotal Phase 3 efficacy and safety data of dupilumab in children aged six months to <6 years with moderate to severe AD. 

Methods: In LIBERTY AD INFANT/PRE-SCHOOL (NCT03346434 part B), a double-blind, placebo-controlled trial, children aged six months to <6 years with moderate to severe AD (Investigator’s Global Assessment [IGA] score ≥3) inadequately controlled with topical therapies were randomized 1:1 to subcutaneous dupilumab every four weeks (q4w) (200mg if baseline weight ≥5–<15kg, 300mg if ≥15–<30kg, randomization stratified by weight) or placebo for 16 weeks. From Day –14, all patients initiated standardized treatment with low-potency topical corticosteroids (TCS). 

Results: 162 patients were randomized (dupilumab/placebo groups, n=83/79); 157 (96.9%; dupilumab/placebo n=82/75) completed 16 weeks of treatment. At Week 16, 27.7%/3.9% (P<0.0001) of patients receiving dupilumab/placebo achieved an IGA score of 0–1 (clear/almost clear), and 53.0%/10.7% (P<0.0001) achieved greater than or equal to 75-percent improvement in Eczema Area and Severity Index (co-primary endpoints). Least squares (standard error) mean percent change from baseline at Week 16 in EASI and weekly averaged worst scratch/itch score in dupilumab/placebo was –70.0%(4.9)/–19.6%(5.1) (P<0.0001) and –49.4%(5.0)/–2.2%(5.2) (P<0.0001), respectively. Improvements were rapid (all statistically significant by Week 4) and continued through the treatment period. Proportions of patients with ≥1 treatment-emergent adverse event (TEAE) were 63.9%/74.4% in dupilumab/placebo groups. Proportions with ≥1 serious TEAE and with TEAE-related treatment discontinuation were 0%/5.1% and 1.2%/1.3%, respectively. The incidence of conjunctivitis (narrow cluster) was 4.8%/0%, and the incidence of skin infection (excluding herpes infection) was 12.0%/24.4% in dupilumab/placebo groups. The most common TEAEs (by Medical Dictionary for Regulatory Activities Preferred Term) were dermatitis atopic (13.3%/32.1%), nasopharyngitis (8.4%/9.0%), upper respiratory tract infection (6.0%/7.7%), impetigo (3.6%/7.7%), and lymphadenopathy (3.6%/7.7%) in dupilumab/placebo groups.

Conclusion: In children aged 6 months to <6 years with moderate to severe AD, dupilumab q4w + low-potency TCS vs placebo + low-potency TCS rapidly and significantly improved AD signs and symptoms. Dupilumab was well tolerated and demonstrated a favorable safety profile, similar to that observed in adults and older children.

Funding: Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.

 

Efficacy and safety of tralokinumab in adolescents with moderate to severe atopic dermatitis: results of the Phase 3 ECZTRA 6 trial

Presenters: Paller A,1 Blauvelt A,2 Weily Soong,3 Imafuku S,4 Hong C,5 Schuttelaar MLA,6 Petra Amoudruz P,7 Kurbasic A,7 Soldbro L,7 Lophaven K,7 Cork M,8 Bewley A,9 Simpson E10

Affiliations: 1Feinberg School of Medicine, Northwestern University, Chicago, IL; 2Oregon Medical Research Center, Portland, OR; 3Allervie Health-Alabama Allergy & Asthma Center, Birmingham, AL; 4Fukuoka University, Fukuoka, Japan; 5University of British Columbia, Vancouver, BC, Canada; 6University Medical Centre Groningen, University of Groningen, The Netherlands; 7LEO Pharma A/S, Ballerup, Denmark; 8University of Sheffield, Sheffield, UK; 9Barts Health NHS Trust, London, UK; 10Oregon Health & Science University, Portland, OR

Background: In adult Phase 3 trials, tralokinumab demonstrated efficacy and safety for AD treatment [Wollenberg A, et al. Br J Dermatol. 2021;184:437-449; Silverberg JI, et al. Br J Dermatol. 2021;184:450-463]. We evaluated tralokinumab efficacy and safety in adolescents with moderate to severe AD in the Phase 3 ECZTRA 6 trial (NCT03526861). 

Methods: Adolescents (aged 12-17 years) were randomized to receive subcutaneous tralokinumab 150 mg (n=100) or 300 mg (n=101), or placebo (n=100) every two weeks. Primary endpoints were Investigator’s Global Assessment (IGA) score 0/1 and greater than or equal to 75-percent improvement in Eczema Area and Severity Index (EASI-75) at Week 16. Patients achieving primary endpoints without rescue treatment were re-randomized for 36 weeks of maintenance treatment. EASI-75, IGA 0/1, and ≥4-point improvement in adolescent pruritus Numerical Rating Scale (NRS) were analyzed using Cochran-Mantel-Haenszel test stratified by geographic region and baseline disease severity. Patients receiving rescue therapy or with missing data were considered non-responders. SCORing AD (SCORAD) and Children’s Dermatology Life Quality Index (CDLQI) were analyzed using a linear mixed model for repeated measurements.

Results: At Week 16, significantly greater proportions of patients receiving tralokinumab (150 mg/300 mg vs placebo) achieved IGA 0/1 (21.4%/17.5% vs 4.3%; P<0.001/P=0.002), EASI-75 (28.6%/27.8% vs 6.4%; P<0.001/P<0.001), and ≥4-point improvement in adolescent pruritus NRS (23.2%/25.0% vs 3.3%; P<0.001/P<0.001). Tralokinumab treatment was associated with greater improvement than placebo in SCORAD (adjusted mean change ± SE: –27.5 ± 2.4/–29.1 ± 2.4 vs –9.5 ± 3.0; P<0.001/P<0.001) and CDLQI (–6.1 ± 0.6/–6.7 ± 0.6 vs –4.1 ± 0.7; P=0.040/P=0.007) from baseline to Week 16. Through Week 16, percentages of adverse events (AEs; 67.3/64.9 vs 61.7), serious AEs (3.1/1.0 vs 5.3), AEs leading to discontinuation (1.0/0 vs 0), and conjunctivitis events (4.1/3.1 vs 2.1) were similar between the tralokinumab and placebo groups. 

Conclusion: At Week 16, tralokinumab 150mg and 300mg every two weeks demonstrated efficacy compared with placebo across primary and secondary endpoints in adolescents with AD. Tralokinumab was well tolerated; efficacy and safety profiles were comparable to those in Phase 3 adult tralokinumab trials.

Funding: The ECZTRA 6 trial was sponsored by LEO Pharma A/S, Ballerup, Denmark.

 

Long-term efficacy of baricitinib 2-mg for the treatment of atopic dermatitis in North America

Presenters: Simpson E1, Boguniewicz M,2 Finklea L,3 Lain E,4 Sun L,5 Cheng S,6 Angle R5, Cardillo T,5 Nunes FP,7* Silverberg JI8

Affiliations: 1Oregon Health and Science University, Portland, OR; 2National Jewish Health, Denver, CO; 3RFSA Dermatology, San Antonio, TX; 4Sanova Dermatology, Pflugerville, TX; 5Eli Lilly and Company, Indianapolis, IN; 6TigerMed, Somerset, NJ; 7Formerly with Eli Lilly and Company, Indianapolis, IN; 8George Washington University, Washington, DC,*Employed with Eli Lilly at the time of study

Background: Baricitinib, an oral, selective Janus Kinase (JAK)1/JAK2 inhibitor, improved disease in adults with moderate to severe atopic dermatitis (AD) in a 16-week placebo-controlled study. We report long-term efficacy of baricitinib 2-mg by integrating a Phase 3 trial (BREEZE-AD5; NCT03435081) and its long-term, open-label extension (BREEZE-AD6; NCT03559270).

Methods: Adults with moderate to severe AD received baricitinib monotherapy in BREEZE-AD5. After Week 16, responders could continue in BREEZE-AD5 while partial and non-responders could transition to baricitinib 2-mg in BREEZE-AD6. Responders from BREEZE-AD5 who later lost response or completed Week 104 were also eligible for BREEZE-AD6. Low-potency topical corticosteroids (TCS) were permitted after Week 16 in BREEZE-AD5 and throughout BREEZE-AD6. Proportions of patients with ≥75% improvement from baseline in Eczema and Severity Index (EASI75), vIGA-AD™ score of 0 or 1 (0, 1), and Dermatology Life Quality Index (DLQI) score ≤5 (among those with baseline score >5), as well as mean SCORing AD (SCORAD) visual analog scales of itch and sleeplessness scores and mean percent change from baseline in EASI score were assessed through 52 weeks of continuous baricitinib 2-mg treatment. Data were censored after TCS rescue during the first 16 weeks. Last observation carried forward was applied to missing data.

Results: This integrated analysis included 146 baricitinib-2-mg-treated patients. Mean baseline EASI score was 26.6. At Weeks 16, 32, and 52, respectively, mean percent change from baseline in EASI score was -50.1%, -59.1%, and -56.8%, and EASI75 responses were observed in 39.6 percent, 51.4 percent, and 48.6 percent of patients. Proportions of patients with vIGA-AD (0, 1) were 27.1 percent, 38.2 percent, and 31.3 percent at Weeks 16, 32, and 52, respectively. Mean SCORAD pruritus score improved from 7.7 at baseline to 4.8 at Week 16 and was maintained at Weeks 32 (3.8) and 52 (4.3). Mean SCORAD sleeplessness score improved from 6.5 at baseline to 3.9 at Week 16 and remained stable through Weeks 32 (3.4) and 52 (3.7). In 129 patients with baseline DLQI >5, 38.6 percent, 48.8 percent, and 44.9 percent had DLQI scores ≤5 at Weeks 16, 32, and 52, respectively, indicating a small or no effect of AD on quality of life.

Conclusion: Baricitinib 2-mg demonstrated long-term efficacy in adults with moderate to severe AD. With long-term therapy (up to 52 weeks), patients treated with baricitinib 2-mg continued to maintain disease control as assessed by decreased skin inflammation and itch and improved sleep and quality of life. 

Funding:Study was sponsored by Eli Lilly and Company, under license from Incyte Corporation.

Disclosures: E. L. Simpson has been a consultant and/or investigator for: AbbVie, Boehringer Ingelheim, Dermavant, Eli Lilly and Company, Galderma, Incyte, LEO Pharma, Merck Sharp & Dohme, Pfizer, Pierre Fabre, Regeneron, and Sanofi Genzyme; M. Boguniewicz has been a consultant and/or investigator for: AbbVie, Eli Lilly and Company, Incyte, Janssen, LEO Pharma, Pfizer, Regeneron, and Sanofi Genzyme; L. Finklea has no disclosures to declare; E. Lain has been an advisory board member, investigator, speaker, and/or consultant for: AbbVie, Allergan, Almirall, Amgen, Arcutis, Athenex, Brickell Biotech, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Galderma, Johnson & Johnson, Kiniksa, LEO Pharma, L’Oreal, Novartis, Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Pulse Biosciences, Regeneron/Sanofi Genzyme, Sebacia, UCB Pharma, and Vyne Therapeutics; S. Chen is an employee of: Tigermed; L. Sun, R. Angle, and T. Cardillo are employees and shareholders of: Eli Lilly and Company; F. P. Nunes is a former employee of: Eli Lilly and Company; J. I. Silverberg has received grants and/or personal fees from: AbbVie, AFYX Therapeutics, Arena Pharmaceuticals, Asana BioSciences, Bluefin, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Luna Pharma, Menlo Therapeutics, Novartis, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi Genzyme. This study was sponsored by Eli Lilly and Company, under license from Incyte Corporation. Medical writing assistance was provided by Ella Lineham, PhD, of ProScribe – Envision Pharma Group, and was funded by Eli Lilly and Company

 

Interim analysis results from a proof-of-concept study for ASLAN004 in adult moderate to severe atopic dermatitis: A double blind, randomized, placebo-controlled study

Presenters: Veverka KA,1 Kobayashi K,1 Menezes J,1 McIntyre N,1 Ward A,1 Armstrong A,2 Guan Thng ST3 and Silverberg JI4

Affiliations: 1ASLAN Pharmaceuticals, Menlo Park, CA and Singapore; 2Department of Dermatology, Keck School of Medicine, University of Southern California Los Angeles; 3Skin Research Institute of Singapore, Agency for Science Technology & Research, Singapore; National Skin Center, Singapore; 4Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC

Background: ASLAN004 is a fully human monoclonal antibody that binds to IL-13Rα1 with high affinity and inhibits IL-4 and IL-13 signaling via the Type 2 cytokine receptor, an important target in atopic dermatitis (AD). 

Objective: To evaluate the emerging safety, tolerability, and efficacy of ASLAN004 in a multiple-ascending dose escalation phase in patients with moderate to severe AD.

Methods: Twenty-five adult patients with moderate to severe AD were recruited from the US, Australia and Singapore and randomized 3:1 in three cohorts to receive once weekly 200, 400 or 600mg of subcutaneous ASLAN004 or matching placebo over eight weeks, with a 12-week recovery period. An interim data readout was conducted after Cohorts 1–3 completed eight weeks of treatment to evaluate various clinical endpoints in a limited number of patients before conducting an expansion cohort (Cohort 4, results reported elsewhere). Endpoints in the interim analysis include change from baseline in Eczema Area Severity Index (EASI) score at week 8 and safety assessments including local tolerability and incidence of adverse events (AEs). [NCT04090229]

Results: Three of 25 patients randomized into Cohorts 1–3 discontinued due to restrictions imposed in response to the COVID-19 pandemic. 18 of the remaining 22 patients in the planned interim data readout completed at least 29 days of dosing and assessment and were evaluable for efficacy. The mean ± SD (n=18) baseline scores were 32.5±11.8 for EASI and 44% had severe Investigator Global Assessment (IGA) scores. At Week 8, mean reductions in EASI from baseline were 50 percent, 74 percent and 76 percent for the 200mg (n=4), 400 mg (n=6) and 600 mg (n=3) ASLAN004 dose groups respectively, compared with 42 percent (n=5) for placebo. Mean reductions of peak pruritus from baseline to Week 8 were 34 percent, 48 percent and 39 percent for 200mg (n=4), 400mg (n=6) and 600mg (n=2) ASLAN004 dose groups respectively, compared with 16% for placebo (n=5). Other secondary endpoints were also improved for ASLAN004 compared with placebo (EASI-50, EASI-75, results reported elsewhere). The proportion of patients with AEs and treatment-emergent adverse events (TEAEs) were similar across ASLAN004 treatment and placebo arms. There were no TEAEs leading to discontinuation in the ASLAN004 treatment groups. 

Conclusion: ASLAN004 was well tolerated, with 400mg and 600mg showing promising efficacy in adults with moderate to severe AD.

Funding: ASLAN Pharmaceuticals Pte Ltd was the sponsor of this study.

Long-term safety data for dupilumab up to four years in an open-label extension study of adults with moderate to severe atopic dermatitis

Presenters: Gooderham M1,2 Wollenberg A,3 Soong W,4 Bissonnette R,5 Xiao J,6 Khokhar FA,6 Marco AR,7 Levit NA,6 Shabbir A6

Affiliations: 1SKiN Centre for Dermatology, Peterborough, ON, Canada; 2Queen’s University, Kingston, ON, Canada; 3Ludwig-Maximilian University, Munich, Germany; 4Alabama Allergy & Asthma Center, Birmingham, AL; 5Innovaderm Research, Montreal, QC, Canada; 6Regeneron Pharmaceuticals, Inc., Tarrytown, NY; 7Sanofi Genzyme, Madrid, Spain

Background: Patients with moderate to severe atopic dermatitis (AD), a chronic systemic inflammatory disease requiring long-term management, often have an inadequate response to topical therapies. Long-term use of systemic immunosuppressants is not recommended due to safety concerns. Here, we extend the dupilumab safety profile in patients with moderate to severe AD from an open-label extension (OLE) study (NCT01949311) to 204 weeks. 

Methods: Adults with moderate to severe AD who had participated in any dupilumab parent study (Phase 1 to 3) were enrolled into the long-term, multicenter OLE study with an initial duration of three years and up to five years in certain countries. Following protocol amendments in June 2017 and January 2018, 114 and 272 patients re-entered the trial, respectively, and 103 and 207 patients having a treatment interruption of greater than eightweeks between study Week 148 and Week 164. During the OLE, patients were treated with 300mg dupilumab weekly (qw). In 2019, patients transitioned to 300 mg every two weeks (q2w) to align with approved dosage. Concomitant treatments for AD, including topical corticosteroid (TCSs) and topical calcineurin inhibitors (TCIs), were permitted. Because the OLE trial lacks a control arm, LIBERTY AD CHRONOS (NCT02260986) 52-week safety results for adults with moderate to severe AD receiving dupilumab 300mg weekly plus TCS were provided as a comparison. Data shown are for the overall study population (N=2,677).

Results: Of the 2,677 patients who enrolled, 2,207 completed treatment up to Week 52, 1,065 up to Week 100, 557 up to Week 148, 362 up to Week 172 and 352 up to Week 204. 240 patients had treatment duration > 204 weeks. Most withdrawals (810 [59.5%]) during the OLE study period were due to dupilumab approval and commercialization in the country in which the patient had enrolled, 114 (8.4%) patients withdrew due to adverse events and 58 (4.3%) withdrew due to lack of efficacy. Exposure-adjusted incidence rates of treatment-emergent adverse events (TEAEs) were lower in this OLE vs the 300mg qw+TCS arm of the 1-year CHRONOS trial (167.5 vs 322.4 number of patients/100 patient-years). In this OLE, 10.4% of patients had ≥ 1 serious TEAEs; 9.8%, ≥ 1 severe TEAEs; 1.2%, ≥ 1 serious TEAE related to study drug; with 3.7% ≥ 1 TEAEs resulting in permanent drug discontinuation. The most common TEAEs observed were nasopharyngitis (28.9%) and conjunctivitis (20.0%, including conjunctivitis, conjunctivitis allergic/bacterial/viral, and atopic keratoconjunctivitis). Among the patients with conjunctivitis TEAEs, 95% were reported as mild/moderate, and 87 percent of conjunctivitis events were recovered/resolved.

Funding: Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.

Conclusion: Data from this OLE study of long-term dupilumab treatment in adult patients with moderate to severe AD extends the previously reported safety profile of dupilumab to 4 years.

 

Oral difelikefalin reduces pruritus in atopic dermatitis

Presenters: Kim BS,1 Tamari M,1 Zamidar L,1 Nograles K,2 Munera C,2 Goncalves J,2 Guttman-Yassky E,3 Lebwohl M,3 

Affiliations: 1Washington University School of Medicine, St. Louis, MO; 2Cara Therapeutics, Stamford, CT; 3Icahn School of Medicine at Mount Sinai; New York, NY

Background: Patients with mild-to-moderate atopic dermatitis (AD) frequently exhibit severe itch, and treatments that specifically target the AD-related pruritus are lacking. Difelikefalin (DFK), a novel, selective kappa-opioid receptor agonist, is being developed for chronic pruritic conditions and has demonstrated significant itch reduction in subjects undergoing hemodialysis. In August 2021, intravenous DFK was approved by the US Food and Drug Administration for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. 

Objective: We evaluated the efficacy and safety of oral DFK in a Phase 2 study of subjects with AD and moderate to severe pruritus.

Methods: A Phase 2, multicenter, randomized, double-blind, placebo (PBO)-controlled study (NCT04018027) was conducted in adults (age 18–80 years) with AD (defined as Investigator Global Assessment ≥2 and body surface area [BSA] ≤30%) and moderate to severe pruritus (defined as Itch Numerical Rating Scale [I-NRS] score ≥5.0) who were inadequately controlled by topical therapy. Subjects received PBO or oral DFK 0.25 mg, 0.5 mg, or 1.0 mg BID for 12 weeks. The primary and key secondary endpoints were change from baseline in weekly mean I-NRS and ≥4-point improvement in weekly mean I-NRS at Week 12, respectively. A subgroup analysis based on lesional severity was conducted in subjects with mild-to-moderate AD. Safety data were summarized descriptively.

Results: In the Phase 2 study, a total of 401 subjects were randomized, with ~64% having mild-to-moderate AD (BSA <10%). At baseline, the mean I-NRS score was 7.8 and the mean BSA was 8.6%. In the overall population, the treatment difference in mean change in I-NRS between the combined DFK group (all doses) and PBO was −0.43 at Week 12 (P=0.144). In subjects with mild-to-moderate AD, a significant difference in I-NRS mean change from baseline was observed at Week 12 (−0.75) in the combined DFK group compared with PBO (P=0.036), and a significantly greater proportion of subjects achieved a ≥4-point improvement in I-NRS (P<0.05). Reduction in itch was observed as early as Week 1. The most commonly reported treatment-emergent adverse events with DFK were abdominal pain, nausea, dry mouth, headache, dizziness, and hypertension.

Conclusion: An unmet need exists for systemic anti-pruritic therapy in mild-to-moderate AD. Results of this Phase 2 clinical study in subjects with AD and moderate to severe pruritus demonstrated that DFK reduced itch severity and was well tolerated. These findings support the role of DFK as a neuromodulatory agent that may be ideally suited for patients with itch-dominant AD. 

Funding: The study was sponsored by Cara Therapeutics, Inc. 

Disclosures: BK: AbbVie, Abrax Japan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Escient Pharmaceuticals, Galderma, GlaxoSmithKline, Granular Therapeutics, Incyte, LEO Pharma, Lilly, Pfizer, Recens Medical, Regeneron, Sanofi, Trevi Therapeutics – consulting. Cara Therapeutics and LEO Pharma – research grant. MT: Nothing to disclose. LZ: Nothing to disclose. KN, CM, & JG: Cara Therapeutics, Inc. – employment.

ML: Mount Sinai – employee. AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB – research funds. Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc., Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica – consultant.

EG-Y: Mount Sinai – employment. AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Galderma, Glenmark/Ichnos Sciences, Innovaderm, Janssen, KAO, Kiniksa, Kyowa Kirin, LEO Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron Pharmaceuticals, and UCB – research funds (grants paid to the institution). AbbVie, Almirall, Amgen, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, LEO Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB, and Ventyx Biosciences – consultant.

 

Tapinarof cream 1% once daily for the treatment of moderate to severe atopic dermatitis in children and adults: the pivotal Phase 3 ADORING clinical program

Presenters: Eichenfield LF,1,2 Silverberg JI,3 Bissonnette R,4 Tallman AM,5 Brown PM,5 Rubenstein DS,5 Piscitelli SC,5 Jett JE5

Affiliations: 1School of Medicine, University of California, San Diego, CA; 2Rady Children’s Hospital, San Diego, CA; 3School of Medicine and Health Sciences, The George Washington University, DC; 4Innovaderm Research Inc., Montreal, QC, Canada; 5Dermavant Sciences, Inc., Morrisville, NC 

Background: There is a need for efficacious non-steroidal topical therapies for atopic dermatitis (AD) without restrictions on duration, extent of use, or application site. Tapinarof is a novel therapeutic aryl hydrocarbon receptor modulating agent (TAMA) in development for the treatment of psoriasis and AD. In a 12-week Phase 2b study, tapinarof cream 1% once daily (QD) demonstrated significant efficacy versus vehicle and was well tolerated in adolescents and adult patients with moderate to severe AD. Furthermore, efficacy was generally maintained through the last study visit, four weeks after completing treatment, warranting further investigation of a potential remittive effect. 

Objective: To assess the efficacy and safety of tapinarof cream 1% QD in children and adults with moderate to severe AD in two pivotal Phase 3 studies (ADORING 1 and 2) and a long-term extension Phase 3 study (ADORING 3).

Results: ADORING 1 and 2 are two identical, Phase 3, multicenter, double-blind, vehicle-controlled, randomized studies. Male or female patients aged ≥2 years, with a clinical diagnosis of AD, a validated Investigator Global Assessment for Atopic Dermatitis™ (vIGA AD) score >3, and body surface area (BSA) involvement ≥5% and ≤35% (excluding the scalp) are randomized 2:1 to tapinarof cream 1% or vehicle cream QD for 8 weeks. The primary efficacy endpoint of ADORING 1 and 2 is the proportion of patients with a vIGA AD score of clear (0) or almost clear (1) and ≥2-grade improvement from baseline to Week 8. Additional efficacy endpoints include assessments on Eczema Area Severity Index, %BSA affected, and Peak Pruritus-Numeric Rating Scale scores from baseline to Week 8. 

Patients who complete ADORING 1 or 2 will have the option to enroll in the 48-week, open-label, long-term extension study, ADORING 3. In ADORING 3, patients entering with vIGA AD score ≥1 receive tapinarof until complete disease clearance (vIGA AD=0). Patients entering with, or achieving, vIGA AD=0 discontinue treatment and are monitored for duration of remittive effect: off-therapy maintenance of vIGA AD score of clear (0) or almost clear (1). Patients with disease worsening (vIGA AD ≥2) are re-treated with tapinarof until vIGA AD=0. Across all studies, safety assessments include adverse events and patient- and investigator-rated local tolerability. 

Conclusion: This comprehensive Phase 3 clinical trial program assesses the efficacy, safety, tolerability, durability, and potential remittive effect of tapinarof cream 1% QD for the treatment of children and adults with moderate to severe AD.

Funding: Funding was provided by Dermavant Sciences, Inc.

 

Two-year maintenance of response with tralokinumab in moderate to severe atopic dermatitis: interim analysis of the ECZTEND open-label extension trial

Presenters: Blauvelt A,1 Lacour JP,2 Toth DP,3 Langley R,4 Warren R,5 Pinto PH,6 Pink A,7 Simpson E,8 Peris K,9 Wollenberg A,10 Gjerum L,11 Fangel S,11 Corriveau J,12 Reich K13

Affiliations: 1Oregon Medical Research Center, Portland, Oregon, United States; 2University Hospital of Nice Côte D’azur, Nice, France; 3Probity Medical Research, Windsor, Ontario, Canada; 4Dalhousie University, Halifax, Nova Scotia, Canada; 5Salford Royal NHS Foundation Trust and NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom; 6Hospital Universitario La Paz, Madrid, Spain; 7St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospitals, London, United Kingdom; 8Oregon Health & Science University, Portland, Oregon, United States; 9Catholic University of the Sacred Heart, Rome, Italy; 10Ludwig Maximilian University of Munich, Munich, Germany; 11LEO Pharma A/S, Ballerup, Denmark; 12LEO Pharma, Madison, NJ, United States; 13University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Background: An ongoing, 5-year, open-label extension trial, ECZTEND (NCT03587805), is evaluating the safety and efficacy of long-term tralokinumab treatment in patients from parent trials with moderate to severe AD. We investigated the 2-year efficacy and safety of continued tralokinumab treatment and the ability to regain response after pausing and reinitiating tralokinumab.

Methods: In ECZTEND, patients received subcutaneous tralokinumab 300mg every two weeks plus optional topical corticosteroids. This analysis included patients who received tralokinumab for the full 52 weeks in the ECZTRA 1 and 2 trials and had been enrolled ≥60 weeks in ECZTEND (as of April 30, 2020). Patients were analyzed in three cohorts, defined by interval between last parent-trial dose and first ECZTEND dose: ≤5 weeks, 6 to 15 weeks, and >15 weeks. Long-term control at 56 weeks in ECZTEND was assessed as percentage improvement from parent-trial baseline in Eczema Area and Severity Index (EASI) and achievement of ≥50%, 75%, and 90-percent improvement in EASI (EASI-50, -75, -90). Worst weekly pruritus Numeric Rating Scale (NRS) and weekly eczema-related sleep interference NRS were also assessed.

Results: 345 patients had ≥60 weeks of enrollment at data cut-off. Median age was 42 years, 59 percent were male, and median AD duration was 30 years at ECZTEND baseline. Median time between last dose in parent trial and first dose in ECZTEND was 63 days. 126, 133, and 86 patients had ≤5 weeks, 6 to 15 weeks, and >15 weeks between tralokinumab doses, respectively. At ECZTEND baseline, median EASI improvement from parent-trial baseline was 88.9 percent, 78.8 percent, and 68.6 percent in patients in the ≤5-week, 6 to 15 week, and >15-week cohorts, respectively. At Week 56 in ECZTEND (2 years of tralokinumab treatment), median EASI improvement was 92.7 percent, 91.7 percent, and 92.7 percent, respectively. Median EASI improvement equivalent to parent-trial levels was maintained for patients continuing treatment with a ≤5-week interval, and was regained by Week 8 for the 6 to 15–week cohort and Week 16 for the >15-week cohort. EASI-50, -75, and -90 response rates after 56 weeks were comparable between cohorts. Sensitivity analyses were consistent with efficacy for all observed patients. At Week 56 in ECZTEND, median (IQR) worst weekly pruritus NRS was 3.0 for all cohorts (mild itch); median (IQR) weekly eczema-related sleep interference NRS was 1.0 in the ≤5-week and 6 to 15–week cohorts, and 1.5 in the >15-week cohort. The adverse event profile was consistent with that in the parent trials and the ECZTEND overall safety population as of April 30, 2020 (n=1174).

Conclusion: Continued tralokinumab treatment was associated with consistent long-term control from parent trial through ECZTEND. Among patients with >5 weeks between last dose in parent trial and first dose in ECZTEND, median improvement in EASI scores equivalent to parent trial levels was regained by Week 12. Tralokinumab provided long-term control of AD extent and severity, improved itch and sleep interference irrespective of the interval between doses, and was well tolerated over 2 years.

Funding: The ongoing ECZTEND clinical trial is sponsored by LEO Pharma A/S, Ballerup, Denmark.

 

Mechanism and proof of concept for a novel, orally delivered, gut-restricted drug candidate for the treatment of atopic dermatitis and other inflammatory diseases

Presenters: Mihaylov Y,1 Maslin D,1 Ramani K,1 Carpenter N,1 Wardwell-Scott L,1Itano A,1 McHale D,1

Affiliations: 1Evelo Biosciences

Background: There is a newly discovered control mechanism for systemic inflammation radiating from the small intestine. Evelo Biosciences is developing pharmaceutical preparations of single strains of gut mucosa-associated microbes that modulate the small intestinal axis (SINTAX TM), enabling systemic inflammation-resolving therapeutic effects with an oral medicine. EDP1815 is an oral pharmaceutical preparation of a single strain of the human commensal Prevotella histicola which is non-replicating and does not colonize the gut, nor alter the microbiome.

Objective: EDP1815 potently attenuates murine models of TH1, TH2, and TH17- inflammation. In-vivo and ex-vivo models demonstrate the mechanism by which SINTAX medicines modulate systemic inflammatory responses through direct action on host cells in the small intestine. We present the efficacy, safety and tolerability of EDP1815 as demonstrated in a Phase 1b clinical proof-of-concept study in participants with atopic dermatitis.

Methods: EDP1815 was evaluated in a Phase 1b randomized-controlled clinical study of 24 participants with mild and moderate atopic dermatitis randomized 2:1 active:placebo (NCT03733353). EDP1815 was administered as 8.0×1011 bacterial cells once daily for 56 days, with follow-up at Day 70. The primary endpoint was safety and tolerability. Efficacy was assessed using the clinician reported outcomes of EASI, SCORAD, IGA and IGA*BSA, and the patient reported outcomes of DLQI, POEM and Pruritus-NRS. Statistical testing was performed on the estimated treatment difference between EDP1815 and Placebo at Day 56, via MMR models.

Results: EDP1815 was well tolerated, with no treatment-related adverse events of moderate or severe intensity, and no serious adverse events. The difference from placebo in percentage reduction from baseline in EASI, IGA*BSA and SCORAD were 52 percent (p=0.062), 65% (p=0.022), and 55 percent (p=0.043) respectively. At Day 70, 44 percent of participants who received EDP1815 achieved EASI-50 compared with 0% in the placebo group; and the proportion achieving an IGA score of 0 or 1 was 31 percent, again compared with 0% in the placebo group. Clinically meaningful changes were also observed in the DLQI and POEM scores

Conclusion: These data provide the first clinical evidence of translation of the activity of a SINTAX medicine candidate in patients with atopic dermatitis. These data, paired with previously reported data for efficacy in psoriasis, support the further development of SINTAX-targeted therapeutics for the treatment of inflammatory diseases. EDP1815 is entering a 16-week Phase 2 study of patients with mild, moderate and severe atopic dermatitis.

Funding: Funding provided by Evelo Biosciences.


CUTANEOUS ONCOLOGY


Adjuvant pembrolizumab versus placebo in high-risk locally advanced cutaneous squamous cell carcinoma: The Phase 3 KEYNOTE-630 Study

Presenters: Schmults C,1 Lee J,2 Schenker M,3 Bratland A,4 Klochikhin M,5 Gifoni M,6 Dmitry K,7 Rivera-Diaz J,8 Chipman M,9 Dzienis M,10 Geiger JL,11 Chang ALS,12 Daniels GA,13 Cohen EEW,13 Joy JY,14 Gumuscu B,14 Yuan J,14 Guminski A15

Affiliations: 1Dana-Farber Cancer Institute, Boston, MA; 2Chris O’Brien Lifehouse, Camperdown, NSW, Australia; 3University of Medicine & Pharmacy of Craiova, Craiova, Romania; 4Oslo University Hospital, Oslo, Norway; 5Yaroslavl Regional SBIH Clinical Oncology Hospital, Yaroslavl, Russia; 6Oncocentro Ceará, Fortaleza, Brazil; 7Oncological Dispensary No. 2 of Ministry of Health of Krasnodar Region, Sochi, Russia; 8Oncologos del Occidente S.A.S, Pereira, Colombia; 9Alfred Health, Melbourne, VIC, Australia; 10Gold Coast University Hospital, Southport, QLD, Australia; 11Cleveland Clinic, Cleveland, OH; 12Stanford University Medical Center, Stanford, CA; 13UC San Diego, La Jolla, CA; 14Merck & Co., Inc., Kenilworth, NJ; 15Royal North Shore Hospital, St Leonards, NSW, Australia

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer, accounting for 20% to 50% of all skin malignancies. Approximately 30 percent of patients with high-risk locally advanced (LA) cSCC develop disease recurrence within five years of standard-of-care surgical resection and adjuvant radiotherapy (RT). Effective treatments are needed to improve outcomes for high-risk LA cSCC. The PD-1 inhibitors cemiplimab and pembrolizumab have demonstrated antitumor activity and manageable safety in LA and metastatic cSCC. The randomized, double-blind, placebo-controlled, Phase 3 KEYNOTE-630 study (NCT03833167) is designed to evaluate adjuvant pembrolizumab in high-risk LA cSCC.

Methods: Patients must have histologically confirmed LA cSCC as the primary site of malignancy and have undergone complete macroscopic resection of all disease (with or without microscopic positive margins). Patients must have ≥1 high-risk feature: histologically involved nodal disease with extracapsular extension with either ≥1 lymph node (LN) >2 cm in diameter or ≥2 LNs involved; any index tumor with ≥2 of the following: tumor ≥4 cm with a depth >6 mm or invasion beyond subcutaneous fat, multifocal perineural invasion for nerves <0.1 mm in diameter (≥3 foci) or any involved nerve ≥0.1 mm in diameter, poor differentiation and/or sarcomatoid and/or spindle cell histology, recurrent disease (recurrence within three years in the previously treated area), or satellite lesions and/or in transit metastases; or any gross cortical bone invasion or skull base invasion and/or skull base foramen invasion. Additional eligibility criteria include ECOG performance status of 0 or 1; receipt of an adequate postoperative dose of hypofractionated or conventional RT, including patients with a BED EQD2 >48 Gy; completion of adjuvant RT ≥4 weeks and ≤16 weeks from randomization; and provision of a tumor sample for PD-L1 testing. Patients are randomly assigned 1:1 to pembrolizumab 400mg every six weeks or placebo for up to one year (9 cycles) or until disease recurrence, unacceptable toxicity, start of new anticancer therapy, or study withdrawal. Randomization is stratified by extracapsular extension, cortical bone invasion, and prior systemic therapy (all, yes vs. no). Primary end point is recurrence-free survival, assessed by the investigator and confirmed by biopsy. Secondary endpoints are overall survival, health-related quality of life, and safety and tolerability. CT/MRI imaging of the tumor and associated draining LNs is performed at screening and every 12 weeks until the end of Year 2. Adverse events (AEs) are monitored throughout the study and for 30 days after treatment end (90 days for serious AEs). AE severity is graded per NCI CTCAE v4.0. Patient-reported outcomes are administered on Day 1 of cycles 1 to 3, and then every 12 weeks until the end of Year 2. Patients in the placebo arm with biopsy-proven disease recurrence within five years may be eligible to cross over to pembrolizumab (≤18 cycles). Patients in the pembrolizumab arm with disease recurrence >6 months after completion of nine cycles of treatment and within five years may be eligible for pembrolizumab retreatment (≤18 cycles). Planned enrollment is ~570 patients. Recruitment is underway in 23 countries. 

Funding: The study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ.

Disclosures: JL reports receiving personal fees from BMS, Sanofi and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ (MSD); and travel support from BioRad. 

MS reports receiving grants for clinical trial activities from MSD, BMS, Roche, Merck Serono, Sanofi, Novartis, Astra Zeneca, Eli Lilly, Saumsung Pharmaceuticals, Mylan, GSK, Abbvie, Astellas, Regeneron, Bayer, Gilead, Tesaro Pharmaceuticals, and Amgen. 

AB reports receiving institutional support from MSD and Sanofi CS reports receiving grants from Castle Biosciences, Regeneron Pharma, Novartis, Genentech, and Merck; receiving non-financial support from NCCN and SCOUT; and other from Castle Biosciences. 

MD reports advisory board roles for MSD and Novartis; receiving honoraria from BMS and Novartis; and receiving educational support from Novartis and Roche. 

JLG reports receiving consulting/advisory board fees from Regeneron and receiving institutional clinical trial funding from Regeneron, Roche/Genentech, and Alkermes. 

ALSC reports being a clinical investigator for Merck for the submitted work and being a clinical investigator and advisory board member for Merck and Regeneron outside the submitted work.

GAD has nothing to disclose. 

EEWC reports receiving compensation for consulting for MSD. 

JYG reports employment at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. 

BG reports employment at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, and is a share/stockholder or has stock options in Merck & Co., Inc., Kenilworth, NJ. JY reports employment at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. 

AG reports advisory board roles for BMS, Pfizer, Merck, Regeneron and Sanofi, and travel support from Astellas, Bristol-Myers Squibb, and Sun Pharmaceutical Industries, Inc.

Appropriate utilization of the prognostic 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma (cSCC) demonstrated by clinical reports and physician evaluation of real-world cases 

Presenters: Farberg A,1 Siegel J,2 Rackley B,2 Fitzgerald A,2 Kurley S,2 Cook R2

Affiliations: 1Baylor Scott & White Health System; 2Castle Biosciences, Inc.

Background: With an unprecedented increase in cSCC incidence over the past three decades, along with the discordance between available staging systems, the 40-GEP test was developed and validated to augment traditional assessment approaches. This test has shown significant metastatic risk stratification independent of clinicopathologic factors and staging systems using these factors. The purpose of this study was to evaluate usage of the 40-GEP test from one year of clinical orders, along with analysis of a clinician survey, in which real-world cases submitted for clinical testing were presented with or without 40-GEP results, to evaluate appropriate utilization of the 40-GEP. 

Objective: Summary metrics of samples received during the first year of clinical availability that met clinical testing criteria were reported. Sixty clinicians having ordered ≥10 40-GEP tests from August 2020-August 2021 were offered survey participation. Six real-world cases, representing the spectrum of those submitted for clinical testing, were presented first without 40-GEP result (pre-test) and then with 40-GEP results (post-test). Clinicians were asked what treatment recommendations they would make for each pre- and post-test patient case. Analyses of responses from the 34 responding clinicians were compared using Wilcoxon Rank or Kruskal-Wallis tests, for each clinical case. 

Results: The 40-GEP demonstrated robust technical reliability with 97.1 percent of samples yielding a reportable result. The distribution of 40-GEP Class calls was as follows: 68.8 percent Class 1 (low risk for metastasis); 28.3 percent Class 2A (moderate risk); 2.9 percent Class 2B (high risk). Cases had at least one high risk factor (average 2.8) and were deemed high (60.5%) or very high risk (39.3%) by current National Comprehensive Cancer Network guidelines, collectively indicative of a high-risk cSCC testing population. Evaluation of clinician responses to each real-world patient case showed diverse pre-test recommendations for baseline assessment and treatment plans, consistent with broad guidelines for this disease. When the 40-GEP test result was considered, clinicians significantly modulated their proposed pre-test treatment plans based on 40-GEP results, including recommendations regarding imaging, sentinel lymph node biopsy, adjuvant therapy, and clinical trial participation (Bonferroni-corrected Wilcoxon Rank tests, p<0.005). Independent of baseline clinicopathological risk, molecular risk assessment by 40-GEP had a significant impact on the overall management intensity proposed by clinicians relative to pre-test planning (Kruskal-Wallis, p<0.05 for all cases). Directionality of these pre- to post-test changes aligned with molecular risk prediction whereby clinicians intensified management strategies for post-test Class 2B cases and deescalated management for patients for post-test Class 1 cases.

Conclusion: Clinicians are ordering the 40-GEP test for the intended use population (cSCC with one or more risk factors). Survey findings revealed that when incorporating 40-GEP testing into their decision-making process for high-risk cSCC patients, clinicians do so in a risk-aligned manner, indicating that this additional information can appropriately assist in management decisions.

Funding: This study was funded by Castle Biosciences, Inc.

 

A comprehensive diagnostic offering workflow increases the rate of actionable results of the 23- and 35-gene expression profile tests for use as ancillary diagnostic tools for difficult-to-diagnose melanocytic lesions

Presenters: Goldberg MS,1,2 Siegel J,2 Russell BH,2 Rogers JH,2 Covington K,2 Oelschlager KM2 Poteet TM2, Wilkinson JK,2 Berg MD,2 K Falkowski K,2 Kurley SJ2, and Kajoian A2 

Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY; 2Castle Biosciences, Inc., Friendswood, TX 

Background: Diagnostic discordance in suspicious melanocytic lesions is well documented and it is particularly prevalent among difficult-to-diagnose cases for which histopathology may be insufficient for a definitive diagnosis. The 23-gene expression profile (GEP) and 35-GEP tests are clinically available objective ancillary tools designed to aid in the differentiation of melanocytic lesions with ambiguous histopathology. The tests are based on algorithms incorporating differential gene expression of 14 or 32 discriminant genes, respectively, to produce results of benign, intermediate, or malignant. With over 35,000 clinical samples tested to date, the 23-GEP has shown accuracy metrics of over 90 percent sensitivity in numerous clinical studies that included patient outcomes (Clarke L, Cancer, 2017; Ko J, Hum Pathol, 2019). However, the 23-GEP historically had ~23% of cases receiving either a technical failure or an intermediate result, which can be perceived as nonactionable. The more recently available 35-GEP test was developed to address this shortcoming and showed both an increased sensitivity in the first validation cohort (Estrada SI, SKIN, 2020) and a decreased nonactionable rate of 8.5 percent in clinical orders. Today, both the 23- and 35GEP are offered from a single laboratory as part of a comprehensive diagnostic offering (CDO) workflow. Clinical samples are processed first through the 23-GEP test, and if a technical failure or intermediate result is received, processed through the 35-GEP. Here we report accuracy metrics from an archival research cohort and actionable result rates from clinical cases from this workflow. 

Methods: The research cohort samples underwent blinded dermatopathology review and were included in the study if they received at least 2 out of 3 diagnostic concordance. Samples were acquired from patients ≥18 years of age under an IRB-approved protocol or were previously submitted for clinical testing for the 31-GEP. The study also included clinical cases submitted for CDO workflow testing reported from June 3 to August 31, 2021.  

Results: The research cohort (n=738) samples subjected to the clinical CDO workflow demonstrated a high level of accuracy, with 94.7 percent sensitivity (95% CI, 92.4–96.8%), 89.5 percent specificity (86.3–92.7%), 90.1 percent positive predictive value (87.7–93.4%), and 94.1 percent negative predictive value (91.4–96.4%). From clinical samples that received CDO workflow testing, the 23-GEP gave an actionable result of benign (55.3%) or malignant (22.5%) in 77.8 percent of cases, which is comparable to past reporting for this test. Nonactionable classifications of the 23-GEP test were 12.9 percent intermediate and 9.4 percent technical failure. These cases were subsequently run on the 35-GEP test, and an additional 22.2 percent of originally submitted cases received an actionable result; the technical failure rate for the 35-GEP test was 0.2 percent. Only 1.1 percent of cases received an intermediate 35-GEP test result. The CDO clinical workflow increased the rate of an actionable report from 77.8 percent to 98.7 percent when compared with 23-GEP testing alone.  

Conclusion: The CDO workflow demonstrated a high level of diagnostic accuracy and has substantially improved reporting of clinically actionable results from a historic and current rate of ~78% to over 98%.  

Funding: This study was funded by Castle Biosciences, Inc.

 

Evidence review of the prognostic 40-gene expression profile test for cutaneous squamous cell carcinoma

Presenters: Goldberg MS,1 Kurley SJ,1 Siegel JJ,1 Fitzgerald A,1 Cook R1

Affiliations: 1Castle Biosciences, Inc. 

Background: In many cancer types, molecular prognostics have significantly impacted patient care. The 40-gene expression profile test (40-GEP) was developed and validated to provide accurate assessment of a patient’s risk for metastasis after diagnosis of cutaneous squamous cell carcinoma (cSCC) with one or more risk factors. Herein, evidence supporting the 40-GEP test, including analytical validity, clinical validity, and clinical utility, are reviewed.

Methods: Analytical validation of the performance of the 40-GEP test included precision experiments to assess inter-assay and intra-assay reliability and the assessment of its technical success rate. Previously published clinical validation data from independent cases with verified clinicopathologic information and known outcomes were assessed by Kaplan-Meier survival analysis and Cox regression analysis. Previously published clinical utility data addressing the impact of the 40-GEP on patient management plans were summarized.

Results: Reliability of the 40-GEP test for class call assignments was verified by demonstration of inter- and intra-assay concordance of 93 percent and 98 percent, respectively. Over a duration of one year, 97.1 percent of all clinically tested samples with sufficient tumor content gave successful, actionable class call outcomes, highlighting the low multi-gene failure rate of the test. Independent validation of the 40-GEP algorithm (n=420) demonstrated statistically significant separation by Class call with 3-year metastasis free survival of 93.9 percent, 80.5 percent, and 47.8 percent for Class 1 (low risk of metastasis), Class 2A (moderate risk), and Class 2B (high risk) cases, respectively. Regardless of the specific risk factor or clinicopathologic risk assessment method (e.g. AJCC-8 or BWH staging) included in the multivariable regression analysis, the 40-GEP demonstrated independent and statistically significant prognostic value with hazard ratios for Class 2A and 2B similar to or beyond that of clinicopathologic factor based systems. Three separate clinical impact surveys (n=596 total clinicians) demonstrated that the prognostic information garnered through the 40-GEP test could aid in cSCC patient management, specifically regarding nodal evaluation, adjuvant radiation therapy, and follow-up. Changes to pre- and post- 40-GEP test management plans for patient vignettes demonstrated that there was a significant and risk-appropriate impact of the 40-GEP test when integrated into decision making. 

Conclusion: The data across the three critical pillars of molecular testing demonstrate the robustness, accuracy and utility of the 40-GEP test. Clinical validity data supports the use of the test as an adjunct to current risk assessment to better evaluate a patient’s metastatic risk. Clinical utility data illustrates that physicians understand 40-GEP test results and how to appropriately integrate these results into their clinical considerations for treatment of cSCC patients with one or more risk factors, ideally leading to a more personalized treatment pathway.Disclosures: Ortho Dermatologics is a division of Bausch Health US, LLC. This abstract was supported by Ortho Dermatologics, Inc., Bridgewater, NJ. Ortho Dermatologics is a division of Bausch Health US, LLC.

Funding: This study was funded by Castle Biosciences, Inc. 

 

Integrating the 31-gene expression profile and clinicopathologic data to determine the disk of sentinel lymph node positivity and distant metastasis-free survival in cutaneous melanoma

Presenters: Martin B,1 Taylor N,2 Whitman E,3 Ann Quick A,1 Bailey C,1 Covington K,1 Vetto J4

Affiliations: 1Castle Biosciences, Incorporated, Friendswood, TX, 2Zitelli and Brodland, P.C., Pittsburgh, PA, 3Atlantic Health System Cancer Care, Morristown, NJ, 4Oregon Health & Science University, Portland, OR. 

Objective: The 31-gene expression profile (31-GEP) test for cutaneous melanoma assesses the risk of sentinel lymph node (SLN) positivity and regional recurrence, distant metastasis, and melanoma-specific survival (MSS) using the primary tumor genetic profile. The purpose of this study was to demonstrate the combined ability of two independently validated algorithms that incorporate the 31-GEP with clinicopathologic features to predict individual SLN positivity risk and distant metastasis-free survival (DMFS).

Methods: Using artificial intelligence techniques, an algorithm to determine the individual likelihood of SLN positivity was developed from 1,398 cases and validated in an independent cohort of 1,674 cases (i31-GEP-SLNB). Next, an algorithm for personalized survival predictions for recurrence-free survival (RFS), DMFS, and MSS was developed from 1581 cases and validated in an independent cohort of 523 cases (i31-GEP-outcomes). To create DMFS risk cut-points that align with NCCN treatment recommendations, the DMFS midpoint between stage IIA and IIB was set as the risk cut-off (82.6%). Those with an i31-GEP-outcomes predicted DMFS higher than the cut-off were classified as low risk of metastasis (LR). Otherwise, they were classified as high risk (HR). To evaluate the prognostic value of using both i31-GEP algorithms, the subset of patients (N=433) not utilized in the development of either algorithm was analyzed first by i31-GEP-SLNB, followed by i31-GEP-outcomes.

Results: The i31-GEP-SLNB predicted that 135 (32.2%) patients had SLN positivity risk <5%. No patient with a predicted risk of <5% had a positive SLN. Kaplan-Meier analysis showed that patients with <5% risk of SLN positivity had DMFS rates of 98.1 percent (median 5.1-years follow-up). Of the 298 patients with an i31-GEP-SLNB predicted risk of ≥5% (median 4.4 years follow-up), 83 (27.9%) had a positive SLN. In patients with ≥5% SLN positivity risk, those with an LR DMFS score predicted by i31-GEP-outcomes had better survival rates than those with an HR DMFS score (92.9% vs. 51.6%). Importantly, even when patients with an LR DMFS score had a positive SLN (n=12), survival outcomes remained high (DMFS: 88.9%). Conversely, those with an HR DMFS score with a negative SLN (n=50) maintained low DMFS rates (DMFS: 55.7%). Using NCCN treatment recommendations, the i31-GEP test identified 45.5 percent (197/433) of patients who could have avoided an SLNB (n=135) or were re-stratified as low (n=12) or high (n=50) risk compared to staging alone.

Conclusion: A combined approach of SLN prediction followed by survival analysis promotes individualized, risk-aligned patient management. Use of the i31-GEP could alter management decisions in 45.5 percent of patients.

Funding: This study was sponsored by Castle Biosciences, Inc.

 

PLATforM: Descriptive analysis from a randomized, Phase 2 study of novel spartalizumab combinations in previously treated unresectable/metastatic melanoma

Presenters: Robert C,1 Schadendorf D,2 Long GV,3 Ascierto P,4 Intagliata S,5 Meier F,6 van der Veldt AAM,7 Ribas A,8 Weber J,9 Solovieff N,10 Louveau AL,11 Boran A,12 Grob JJ,13 Dummer R14

Affiliations: 1Department of Medicine, Gustave Roussy and Paris-Sud-Paris-Saclay University, Villejuif, France; 2Department of Dermatology, University Hospital Essen, Essen, Germany; 3Department of Medical Oncology, Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia; 4Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori-IRCCS Fondazione “G. Pascale”, Naples, Italy; 5Department of Medical Oncology, ASST Papa Giovanni XXIII, Bergamo, Italy; 6Department of Dermatology, University Hospital Carl Gustav Carus, University of Dresden, Dresden, Germany; 7Departments of Medical Oncology and Radiology & Nuclear Medicine, Erasmus University Medical Center, Rotterdam, Netherlands; 8Department of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA; 9Department of Medical Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY; 10Novartis Institutes for Biomedical Research, Cambridge, MA; 11Novartis Pharma SAS, Paris, France; 12Global Drug Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ; 13Dermatology and Skin Cancer Department, Aix-Marseille University, Marseille, France; 14Department of Dermatology, University Hospital Zürich Skin Cancer Center, Zürich, Switzerland

Background: There is an unmet medical need for patients (pts) with advanced melanoma who progress on immunotherapy/targeted therapy. Spartalizumab is an anti-PD-1 humanised monoclonal antibody (mAb) that may combine effectively with novel compounds to restore anti-tumour responses in PD-1 refractory disease. This is an analysis of a Phase 2, randomised, two-part, multicentre, open-PLATforM (NCT03484923) study in pts with unresectable/metastatic melanoma progressing after prior anti-PD-1/L1 therapy. 

Methods: The primary endpoint was overall response rate (ORR) per RECIST v1.1; secondary endpoints included duration of response and biomarker assessments. The selection phase comprised four arms combining spartalizumab with ieramilimab (anti-LAG3 mAb; Arm 1), capmatinib (2), canakinumab (3) or ribociclib (4). An adaptive design during the selection phase allowed dropping arms for futility, adding new arms and selecting arm(s) for expansion. Bayesian methodology was used for futility and efficacy assessments at each interim analysis (IA). 

Results: As of February 1, 2021, 175 pts were randomized; 45, 43, 43 and 44 pts in each arm, respectively. Median age was 59 yrs, 57 percent received ≥2 prior therapies. Overall, 166/175 pts discontinued treatment, primarily due to progressive disease (65%). ORRs in Arms 1–4 were n = 3/45 (7%), 2/43 (5%), 2/43 (5%) and 3/44 (7%), respectively. All arms crossed the specific futility probability threshold and were declared futile at previous IAs. In Arm 1, 6 pts had LAG-3+ melanoma at baseline (≥5% + tumour cells by IHC), of which two pts had a partial response, both ongoing for 23 months. Overall, grade ≥3 adverse events occurred in 59 percent of pts (53%, 51%, 36%, 93% in Arms 1–4, respectively). There were 14 on-treatment deaths; 5/45 in Arm 1, primarily due to melanoma progression (4/45).

Conclusion: Although all tested combinations have been declared futile, pts with LAG-3+ melanoma may be more likely to respond to spartalizumab + ieramilimab treatment. Consequently, Arm 1A (spartalizumab +ieramilimab) was opened to recruit pts with previously treated unresectable/metastatic LAG-3+melanoma. Arm 1A has fully recruited 21 pts. The data cut-off (DCO) for the interim analysis for Arm1A was 28-Oct-2021 based on the 21 pts and the analysis is currently ongoing.

Funding: This study is sponsored by Novartis Pharmaceuticals Corporation.

Disclosures: CR reports a consultant or advisory role with Bristol Myers Squibb, MSD, Roche, Novartis, Sanofi, Pierre Fabre, and Pfizer.

 

Tumor burden in patients with locally advanced basal cell carcinoma and metastatic basal cell carcinoma following treatment with sonidegib: Results of the 42-month BOLT study

Presenters: Migden M,1 Farberg AS2, Spencer J,3 Kiecker F,4 Guminski A5-7 Gebauer K,8,9 Loquai C10, Robert C,11 Squittieri N,12 Dummer R13

Affiliations: 1University of Texas MD Anderson Cancer Center, Departments of Dermatology, Division of Internal Medicine, and Head and Neck Surgery, Division of Surgery, Houston, TX; 2Baylor University Medical Center, Division of Dermatology, Dallas, TX; 3Spencer Dermatology and Skin Cancer Center, St Petersburg, FL; 4Department of Dermatology, Venereology, and Allergology, Charité Universitätsmedizin Berlin, Edmund-Lesser-Haus, Berlin, Germany; 5Department of Oncology, Royal North Shore Hospital, St Leonards, Australia; 6Melanoma Institute Australia, The University of Sydney, Sydney, Australia; 7Mater Hospital, Sydney, Australia; 8University of Western Australia, Perth, Western Australia, Australia; 9Probity Medical Research, Waterloo, Ontario, Canada; 10Department of Dermatology, University Medical Center Mainz, Mainz, Germany; 11Department of Dermatology, Institut Gustave Roussy and Paris-Saclay University, Villejuif, France; 12Medical Affairs Oncology and Long Term Care, Sun Pharmaceutical Industries, Inc., Princeton, NJ; 13Department of Dermatology, University of Zürich, Skin Cancer Center, University Hospital, Zürich, Switzerland

Background: Sonidegib, a Hedgehog pathway inhibitor, is approved for the treatment of locally advanced basal cell carcinoma (laBCC) in the US, EU, Switzerland, and Australia and metastatic BCC (mBCC) in Switzerland and Australia not amenable to curative surgery or radiation therapy. We evaluated tumor burden through 42 months of treatment with sonidegib. 

Methods: BOLT was a randomized, double-blind, multicenter Phase 2 study with patients randomized 1:2 to receive once daily sonidegib 200 or 800mg orally, respectively. Efficacy assessments included objective response rate (ORR), duration of response (DOR), partial response (PR), stable disease (SD), and progression-free-survival (PFS) per central review. Safety assessments included adverse event (AE) monitoring.

Results: At 42 months, ORRs (95% confidence interval [CI]) in patients with laBCC (n=66) and mBCC (n=13) receiving sonidegib 200mg were 56.1 percent (43.3%–68.3%) and 7.7 percent (0.2%–36.0%). In patients with laBCC, PR and SD were 51.5 percent and 34.8 % vs 7.7% and 84.6 percent in patients with mBCC, respectively. Median DOR (95% CI) was 26.1 (not estimable [NE]) and 24.0 (NE) months for patients with laBCC and mBCC, respectively. Median (95% CI) PFS for patients with laBCC and mBCC was 22.1 (NE) and 13.1 (5.6–33.1) months, respectively. Overall decrease in best percent change from baseline in target lesions for patients with laBCC was 92.3% and 91.7 percent in patients with mBCC. AEs were mostly grade 1–2.

Conclusion: Through 42 months of treatment, sonidegib demonstrated durable tumor response and substantial reduction in tumor burden in patients with laBCC and mBCC.

Funding: This study was funded by Sun Pharmaceutical Industries, Inc.

Disclosures: MM has participated on advisory boards and received honoraria from Genentech; Novartis Pharmaceuticals Corporation; Sun Pharmaceutical Industries, Inc.; and Regeneron Pharmaceuticals. 

ASF has participated on advisory boards and received honoraria from Ortho-dermatologics; Sensus; and Sun Pharmaceutical Industries, Inc. 

JS has nothing to disclose. 

FK reports grants and personal fees from Amgen, BMS, MSD, Novartis, Pierre Fabre, Roche, and Sanofi. 

AG has participated on advisory boards for Bristol-Myers Squibb, Pfizer, and Sanofi; received honoraria from Novartis Pharmaceuticals Corporation; and received travel support from Astellas and Bristol-Myers Squibb. 

KG has participated on advisory boards and received education grants from Abbvie; Janssen Pharmaceutica; Sanofi Genzyme; and Sun Pharmaceutical Industries, Inc.; and been an investigator for Abbvie; Janssen Pharmaceutica; Leo; Sun Pharmaceutical Industries, Inc.; and UCB. 

CL acted as a speaker for, participated in an advisory board for, and received honoraria from Bristol-Myers Squibb, Roche, Novartis, and Merck Sharp & Dohme. 

CR has received consulting fees from Amgen, Array BioPharma, Bristol-Myers Squibb, Merck, Merck Serono, Novartis, Pierre Fabre, and Roche. 

NS is an employee of Sun Pharmaceutical Industries, Inc. 

RD has participated on advisory boards and consulted for Amgen; Bristol-Myers Squibb; Catalym; Merck Sharpe and Dohme; Novartis Pharmaceutical Corporation; Pierre Fabre; Roche; Sanofi; Second Genome; Sun Pharmaceutical Industries, Inc.; and Takeda.


HAIR


Clinical efficacy of the oral JAK3/TEC inhibitor ritlecitinib (PF-06651600) and patients’ perception of improvement in alopecia areata: results from the ALLEGRO Phase 2b/3 trial

Presenters: Guttman-Yassky E,1 Ito T,2 Jabbari A,3 Mackay-Wiggan J,4 Lejeune A,5, Wolk R,6 Wajsbrot D,7 Zwillich SH6

Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY, 2Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan, 3Department of Dermatology, University of Iowa, Iowa City, IA, 4Siperstein Dermatology Group, Boynton Beach, FL, 5Pfizer, Paris, France, 6Pfizer, Groton, CT, 7Pfizer, New York, NY

Background: The ALLEGRO Phase 2b/3 trial was a randomized, double-blind, placebo-controlled, 48-week study investigating the efficacy and safety of ritlecitinib, an oral JAK3/TEC inhibitor, in patients with alopecia areata (AA). This analysis evaluated the correlation between clinician-assessed efficacy (Severity of Alopecia Tool [SALT]) and Patient’s Global Impression of Change (PGI-C).

Methods: Patients ≥12 years old with AA and ≥50% scalp hair loss received daily ritlecitinib or placebo for 24 weeks, with or without a 4-week loading dose: 200/50mg, 200/30mg, 50mg, 30mg, 10mg, or placebo. Patients randomized to placebo switched to active therapy after Week 24. Change from baseline in SALT score (CFB-SALT), proportion of patients with PGI-C response of ‘moderately improved’ or ‘greatly improved’, and correlation between CFB-SALT and PGI-C score (Spearman coefficients [r]) were evaluated at Weeks 24 and 48. Safety was monitored throughout.

Results: 718 patients were randomized to 200/50mg (n=132), 200/30mg (n=130), 50mg (n=130), 30mg (n=132), 10mg (n=63), or placebo (n=131). In these groups, the mean CFB-SALT at Week 24 were −36.5, −29.2, −33.3, −23.6, −4.2, and −5.1 (P<0.000001 vs. placebo for first 4 groups), and the proportions of patients with PGI-C response were 53.2, 47.1, 49.6, 42.1, 11.7 and 9.2% (P<0.000001 vs placebo for first 4 groups). The mean CFB-SALT at Week 48 in the 200/50mg, 200/30mg, 50mg, 30mg, and 10mg groups improved to −47.2, −39.6, −48.6, −38.5, and −12.5, respectively, and the proportions of patients with PGI-C response improved to 58.1, 52.0, 56.0, 49.2, and 16.4%. CFB-SALT and PGI-C scores were highly positively correlated at Weeks 24 (r=0.827) and 48 (r=0.792). Incidence of treatment-emergent adverse events was similar across groups at Weeks 24 (69.4–75.4%) and 48 (75.8–84.7%), with most being mild-to-moderate.

Conclusion: CFB-SALT and proportions of patients with PGI-C response were greater in the 200/50mg, 200/30mg, 50mg, and 30mg dose groups at Week 24 compared with placebo. Clinician-assessed efficacy and patients’ perception of improvement at Weeks 24 and 48 were highly correlated.

Funding: This study was sponsored by Pfizer.

Disclosures: EGY declares receiving institutional grants from AbbVie, Asana BioSciences, Celgene, Dermavant, Dermira, DS Biopharma, Eli Lilly, Galderma, Glenmark, Innovaderm Research, Janssen, LEO Pharma, Novan, Novartis, Pfizer, Ralexar Therapeutics, Regeneron, and Union Therapeutics, and receiving honoraria and/or consultation fees from AbbVie, Allergan, Amgen, Asana Biosciences, Celgene, Concert, Dermira, DS Biopharma, Eli Lilly, EMD Serono, Escalier Biosciences, FLX Bio, Galderma, Glenmark, Kyowa, LEO Pharma, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron, Sanofi Aventis, and Union Therapeutics. 

TI declares serving as a consultant for Eli Lilly and Pfizer. 

AJ declares receiving institutional grants from Arena Pharmaceuticals, InSilico Medicine, and Pfizer, and receiving honoraria and/or consultation fees from Pfizer. 

JMW declares receiving institutional payment for study-related costs from Concert Pharmaceuticals and Pfizer, and serving as a consultant for Concert Pharmaceuticals, Eli Lilly, and Pfizer. 

AL, RW, DW, and SZ are employees of Pfizer and hold stock or stock options in Pfizer. Medical writing support was provided by David Wateridge, PhD, of Engage Scientific Solutions and was funded by Pfizer.

 

Long-term efficacy of a nutraceutical supplement for promoting hair growth in perimenopausal, menopausal and postmenopausal women with self-perceived thinning hair

Presenters: Ablon G1, Kogan S,2 Isabelle R2

Affiliations: 1Ablon Skin Institute and Research Center, Manhattan Beach, CA, 2Nutraceutical Wellness Inc., New York, NY

Objective: Hair loss in women increases with age and menopause. Hormonal changes of menopause are associated with decreased hair growth rate as well as percentage of hairs and time spent in anagen phase. Here, we present results of a 12-month study assessing the efficacy of a nutraceutical supplement in promoting hair growth in perimenopausal, menopausal and postmenopausal women with self-perceived thinning hair.

Methods: This was a 6-month randomized, double-blind, placebo-controlled trial with a 6-month open label extension phase, whereupon placebo subjects were crossed over to active treatment. The interim 6-month results were previously reported showing statistically significant improvements in hair growth and shedding compared to placebo. The full 12-month study period, including the extension phase, consisted of six clinic visits at baseline, Day 90, 180, 270 and 360. Phototrichograms were obtained of the target area during each visit via macrophotography for hair count analysis. Hair wash shed count was also conducted at each visit. During each clinic visit, two-dimensional standardized global photographs were obtained of the entire head, hair and target region. Two-D images were used to assist a blinded investigator in grading general hair growth and hair quality (texture, shine, dryness, scalp coverage, hair brittleness and overall appearance) improvement from baseline.

Results: Sixty (33 active and 27 placebo) women completed both the randomized and open-label extension phases. Subjects had an overall mean age of 55.2 (+/- 6.6) years with no significant differences between groups. Among subjects who received the active supplement for 12 months, the mean number of terminal hairs progressively increased from 68.1 at Day 0 to 77.18 at Day 360, corresponding to a significant 13.4 percent improvement (p<0.0001). Global hair growth improvement ratings increased significantly 43% from Day 90 to 180 (p<0.001) and 25 percent from Day 90 to 360 (p<0.05). Global hair quality improvement ratings significantly increased by 24% from Day 90 to 180 (p<0.05) and by 37 percent from Day 90 to 360 (p<0.005). Subjects who were initially in the placebo group had a 5.1 percent increase in hair growth (p<0.001) and a 39% decrease in shedding (p<0.0001) from day 180 to 360 when they were switched over to the active treatment. Global hair growth improvement ratings across 6-month of active treatment for this group increased by 30 percent (p<0.05) versus 11 percent when they were taking placebo (p>0.05). Global hair quality improvement ratings significantly increased by 40 percent (p<0.001) versus 11% when they were taking placebo (p>0.05). Daily administration of the nutraceutical supplement was well-tolerated.

Conclusion: The results of this study showed significant and progressive improvements in hair growth during 6 and 12 months, demonstrating the ability of a nutraceutical supplement to effectively improve hair growth and quality in peri-, menopausal and postmenopausal women with thinning hair.

Disclosures: Dr. Ablon received a research grant for the study from Nutraceutical Wellness LLC. All other authors are employees by Nutraceutical Wellness, LLC.


MISCELLANEOUS


Overview of ongoing and upcoming clinical trials in autoimmune blistering diseases: Pemphigus uulgaris and pemphigus foliaceus (ADDRESS and ADDRESS+) and bullous pemphigoid

Presenters: Joly P,1 Bata-Csorgo Z,2 Hertl M,3 Hall R,4 Werth V,5 Sinha AA,6 Seiffert-Sinha K,6 Goebeler M,7 Stoevesandt J,7 Verheesen P,8 Stoykov I,8 Siluk T,8 Schmidt E9

Affiliations: 1Department of Dermatology, Rouen University Hospital, Rouen, France; 2Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary; 3Department of Dermatology and Allergology, Philipps-Universität Marburg, Marburg, Germany; 4Department of Dermatology, Duke University School of Medicine, Durham, North Carolina, United States; 5Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States; 6Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States; 7Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany; 8Argenx, Ghent, Belgium; 9Department of Dermatology, University of Lubeck, Lubeck, Germany

Background: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) belong to the heterogenous group of autoimmune diseases and are clinically characterized by mucosal erosions and/or cutaneous blisters and erosions. IgG autoantibodies primarily target desmoglein (Dsg)-3 in PV and both Dsg-1 and Dsg-3 in the mucocutaneous variant of PV, while PF is attributed exclusively to autoimmunity against Dsg-1. Bullous pemphigoid (BP) is an autoimmune blistering disease, characterized by subepidermal blisters and mediated by IgG autoantibodies against BP180 (type XVII collagen) and BP230 structural proteins of the dermal-epidermal junction. 

The neonatal Fc receptor (FcRn) rescues IgG from lysosomal degradation, thereby increasing availability of circulating IgGs. Efgartigimod is a human IgG Fc fragment engineered to block FcRn, reducing the serum level of circulating IgGs, including pathogenic IgG autoantibodies. In a recent Phase 2 trial, efgartigimod decreased serum concentrations of anti-Dsg-3 and anti-Dsg-1 IgG autoantibodies in 34 patients with mild to moderate PV or PF (Goebeler M, et al. Br J Dermatol. 2021.). Total IgG and anti-desmoglein autoantibody reductions were associated with improved Pemphigus Disease Area Index (PDAI) scores. Disease control (DC) was achieved by 28/31 (90%) patients receiving efgartigimod either as monotherapy or as add-on to prednisone after a median of 17 days. Complete clinical remission (CR) was achieved by 14/22 (64%) patients receiving combined treatment of efgartigimod and prednisone 0.1–0.5 mg/kg/day. Efgartigimod was well tolerated, and most adverse events were mild. 

Based on these results, a Phase 3 trial of efgartigimod was launched in patients with PV and PF. ADDRESS is a multicenter, randomized, double-blind, placebo-controlled trial evaluating efficacy and safety of efgartigimod in patients with PV or PF (ClinicalTrials.gov; NCT04598451). ADDRESS+ is an open-label extension trial designed to evaluate long-term safety and efficacy of efgartigimod in patients who participated in the ADDRESS trial (ClinicalTrials.gov; NCT04598477). Here we provide an overview of the ADDRESS and ADDRESS+ trials and bring awareness to an upcoming phase 2/3 trial of efgartigimod in patients with BP.

Methods: ADDRESS and ADDRESS+ eligibility criteria include clinical diagnosis with PV or PF, age ≥18 years, and PDAI score ≥15. A total of 150 patients (126 PV and 24 PF) are undergoing randomization (2:1) to receive subcutaneous efgartigimod co-formulated with PH20 or placebo/PH20 on top of oral prednisone (or equivalent). Primary endpoint is the proportion of patients with PV who achieve complete remission on minimal therapy (CRmin) within 30 weeks. Secondary endpoints include: proportion of patients with PV or PF achieving CRmin within 30 weeks, time to CR, and time to DC. In ADDRESS+, treatment continuation will be based on clinical status at time of rollover: no efgartigimod if CRmin has been achieved, weekly efgartigimod PH20 SC if CRmin has not been achieved, new treatment cycle in case of treatment failure or flare after CRmin. Safety and long-term remission will be studied in ADDRESS+.

Results: More details on ADDRESS and ADDRESS+ are available on ClinicalTrials.gov (ADDRESS: NCT04598451; ADDRESS+: NCT04598477). More details on the Phase 2/3 trial in BP will be available soon.

Funding: The Phase 3 ADDRESS trial is funded by argenx. 

Disclosures: Efgartigimod is an investigational agent that is not currently approved for use by any regulatory agency.


PRURITUS


A Phase 2b/3, randomized, placebo-controlled, 2-Arm trial evaluating oral nalbuphine extended release for pruritus relief in prurigo nodularis: The PRISM study protocol

Presenters: Brett-Smith H,1 Good J,2Forbes W,2 Buckley P,2 Stander S,3

Affiliations: 1Formerly of Trevi Therapeutics, New Haven, CT; 2Trevi Therapeutics, New Haven, CT; 3Center for Chronic Pruritus, University Hospital Münster, Münster, Germany

Background: Clinical trial population sizes are traditionally established using statistical power calculations, but uncertainty is common, particularly when controlled trial results are unavailable and observational data are limited. For prurigo nodularis (PN), controlled data describing response rates to specific therapies are only now becoming available. One statistical approach increasingly used to address this challenge is a sample size re-estimation (SSRE) based on interim results from an ongoing trial. This protocol summary describes an SSRE for a clinical trial evaluating oral nalbuphine extended release (NAL ER) in PN. Phase 2b/3 Pruritus Relief Through Itch Scratch Modulation (PRISM) is a two-part, one-year, double-blind, placebo-controlled trial evaluating NAL ER 162mg twice daily in PN-related pruritus.

Objective: To address concerns regarding reliability of treatment effectiveness estimates from a previous small NAL ER study in PN, the statistical analysis plan for the PRISM study was modified to include a mid-course SSRE procedure, as described previously (Mehta CR, Pocock SJ. Stat Med. 2000:1-6). The statistical analysis plan was modified when <10 subjects were randomized into PRISM.

Methods: This approach protects study alpha by prespecifying three categories of potential interim findings and requiring a prior commitment from the sponsor based on the outcome category into which the interim results fall. The three categories rely on the observed conditional power (CP) during the interim analysis. If the SSRE interim CP is ≤0.39, it is considered “unfavorable” and would lead to study discontinuation unless the sponsor had prespecified a large increase in sample size and was willing to commit to the associated risk at the time the SSRE plan was developed. A CP >0.4 and <0.9 is considered “promising” and may lead to an increase in sample size as prespecified in the analysis plan without loss of alpha. A CP ≥0.9 is “favorable,” leading to study completion without any change. The interim analysis must be performed by an independent, unblinded statistician. The sponsor’s response is constrained by the prespecified plan, which specifies the increase in study size resulting from a CP in the “promising” zone.

Results: The PRISM SSRE analysis was to be performed after approximately 50 percent of the subjects (n=120) completed the Week 14 primary endpoint assessment or discontinued early. The prespecified analysis was discussed at a closed session of the study’s data safety monitoring board, which reported one of the following statements based on the CP results: 1) “favorable” zone: “carry on”; 2) “promising” zone: “increase sample size to 360” (360 was prespecified in the SSRE amendment to the statistical analysis plan and preselected by the sponsor per Mehta and Pocock); or 3) “unfavorable” zone: “stop the study due to an unfavorable safety and/or efficacy observation”. This method preserves the overall alpha value; the final analysis will use conventional tests without weighing the Stage 1 and 2 results or adjusting the alpha. 

Conclusion: This PRISM study protocol summary describes an SSRE methodology for a clinical trial based on interim data, providing valuable information for future dermatologic studies to ensure that enrolled subjects are receiving the most current and effective treatments.

Funding: Funding toward this study was received from Trevi Therapeutics.

Disclosures: HBS: Employee of Trevi Therapeutics from September 2017 to July 2021.

JG, PB, and WF: Employees of Trevi Therapeutics

SS is an investigator for Almirall, Dermasence, Kiniksa, Galderma, GSK, Menlo Therapeutics, Novartis, Sanofi, Trevi Therapeutics, and Vanda Pharmaceuticals and is a consultant and/or member of the advisory board for AbbVie, Almirall, Beiersdorf, Bellus Health, Benevolent, Bionorica, Cara Therapeutics, Clexio Biosciences, DS Biopharma, Escient, Galderma, Grünenthal, Kiniksa, Leo, Lilly, Menlo Therapeutics, Novartis, Pfizer, Sanofi, Trevi Therapeutics, P.G. Unna Academy, and Vifor.


PSORIASIS


A pooled analysis of randomized, controlled, Phase 3 trials investigating the efficacy and safety of a novel, fixed-dose calcipotriol and betamethasone dipropionate cream for the topical treatment of plaque psoriasis

Presenters: Pinter A1 Green L,2 Selmer J,3 Praestegaard M,3 Gold L,4 Augustin M5

Affiliations: 1University Hospital Frankfurt am Main, Dept. of Dermatology, Frankfurt am Main, Germany; 2George Washington University School of Medicine, Washington DC; 3MC2 Therapeutics, Hørsholm Denmark; 4Dermatology Clinical Research, Henry Ford Health System, Detroit, Michigan; 5University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Background: Calcipotriol and betamethasone dipropionate (50mcg/g CAL and 0.5mg/g BDP) cream (CAL/BDP cream) is based on PAD Technology which for the first time has enabled the development of an easy to apply water-containing cream formulation of CAL and BDP. This pooled analysis analyzes the combined efficacy and safety from two Phase 3 studies conducted in the United States and Europe. 

Methods: CAL/BDP cream was evaluated in two head-to-head, Phase 3, randomized, multicenter, investigator-blind, parallel-group trials comparing the efficacy and safety of CAL/BDP cream to vehicle and an active comparator (50 mcg/g CAL and 0.5mg/g BDP gel/topical suspension (TS)) in adults with psoriasis vulgaris. Eligible participants were adults with a clinical diagnosis of plaque psoriasis involving the trunk and/or limbs. Additional key inclusion criteria included a treatment area involving between 2% and 30% of the body surface area and a physician global assessment (PGA) score of mild or moderate disease severity. Eligible participants were randomly assigned into three treatment groups with a ratio of 3:1:3 for treatment with CAL/BDP cream, matching vehicle, and CAL/BDP gel/TS. Participants were instructed to apply the treatment topically once daily to affected areas for up to eight weeks. Statistical analyses were based on a modified intention-to-treat population (n=1271), which included all randomized participants who had at least one efficacy assessment after the baseline visit. 

Results: The percentage of subjects achieving PGA treatment success at Week 8 was statistically significantly higher in the CAL/BDP cream group (43.2%) compared to the CAL/BDP gel/TS group (31.9%) (p<0.0001). Moreover, these statistically significant differences in PGA between CAL/BDP cream and CAL/BDP gel/TS were observed as early as Week 4 (p=0.0001). The mean percent reduction in mPASI score from Baseline to Week 8 was statistically greater for CAL/BDP cream (64.6%) than CAL/BDP gel/TS (56.4%) (p<0.0001). The difference in mPASI treatment effect between CAL/BDP cream and CAL/BDP gel/TS was statistically significant as early as Week 1 (p=0.0009). In addition, the proportion of subjects obtaining mPASI75 was greater in the CAL/BDP cream group than in the CAL/BDP gel/TS group at Week 4 (22.1% vs. 13.7%) (p=0.0004) and at Week 8 (44.3% vs. 34.5%) (p=0.0011). The mean DLQI improvement from Baseline, at Week 8, was significantly greater for CAL/BDP cream (6.5 points) compared to CAL/BDP gel/TS (5.6 points) (p<0.0001). CAL/BDP cream was well tolerated and comparable to CAL/BDP gel/TS with no adverse drug reactions with a frequency being >1%, associated with the CAL/BDP cream.

Conclusion: The present analysis of pooled data from two randomized, controlled Phase 3 trials investigated the efficacy and safety of a CAL/BDP cream for the topical treatment of psoriasis. The results demonstrated statistically significant greater efficacy in favor of CAL/BDP cream for all efficacy endpoints, including PGA treatment success, mPASI, and PASI75 compared to CAL/BDP gel/TS. Based on the unique combination of high efficacy, favorable safety and convenience of treatment in a single product, CAL/BDP cream can be considered a first-line topical therapy of psoriasis.  

Funding: Funding came from MC2 Therapeutics.

 

Bimekizumab efficacy and safety up to two years in patients with moderate to severe plaque psoriasis switching from ustekinumab: results from the interim BE BRIGHT open-label extension trial

Presenters: Leonardi C,1 Sator PG,2 Morita A,3 Kokolakis G,4 Blauvelt A,5 Warren R,6 Cuyper DD,7 Madden C,8 Vanvoorden V,7 Wang M,8 Papp K9 

Affiliations: 1Central Dermatology and Saint Louis University School of Medicine, St. Louis, Missouri; 2Department of Dermatology, Clinic Hietzing, Vienna, Austria; 3Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 4Psoriasis Research and Treatment Center, Charité-Universitätsmedizin, Berlin, Germany; 5Oregon Medical Research Center, Portland, Oregon; 6Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK; 7UCB Pharma, Brussels, Belgium; 8UCB Pharma, Raleigh, North Carolina; 9Probity Medical Research and K Papp Clinical Research, Waterloo, Ontario, Canada

Background: As patients with psoriasis switch biologics due to inadequate response or adverse events, it is important to determine whether switching biologics is safe and effective.1 Here, we report efficacy and safety data up to two years for patients from the BE VIVID (NCT03370133) Phase 3, double-blinded, active comparator-controlled trial who switched from ustekinumab (UST) to bimekizumab (BKZ), without washout, upon entering the BE BRIGHT (NCT03598790) open-label extension (OLE).2 Data for patients who received continuous BKZ are included for comparison. 

Methods: Patients were initially randomized to UST 45mg/90mg (by weight) at Weeks 0/4, then every 12 weeks or BKZ 320mg every four weeks (Q4W) through Week 52 in BE VIVID, and subsequently entered the OLE. Upon entering the OLE, all patients were re-randomized to BKZ 320mg Q4W or every eight weeks (Q8W) based on PASI90 (≥90% improvement from baseline in Psoriasis Area and Severity Index) response at Week 52.

Data are reported through Week 52–100 (OLE Weeks 0–48). We report PASI100 responses for patients who switched from UST to BKZ (UST/BKZ switchers) or continued to receive BKZ (BKZ/BKZ) upon entering the OLE. PASI90 and PASI100 responses are presented for UST/BKZ switchers who were PASI90 non-responders at the end of BE VIVID (Week 52). Data are presented by initial BE VIVID randomization group (BKZ or UST) regardless of BKZ OLE maintenance dosing regimen. Data are reported using non-responder imputation (NRI). Safety data are also reported.

Results: 136/141 UST-randomized and 276/283 BKZ-randomized patients who completed BE VIVID entered the OLE. Upon entering the OLE at Week 52, 44.9 percent UST and 73.6 percent BKZ patients had achieved PASI100.  For all UST/BKZ switchers, PASI100 response increased to 65.4 percent at Week 56 after switching to BKZ and was comparable to BKZ/BKZ patients at Week 68 through Week 100 (UST/BKZ switchers: 78.7 percent and 69.9 percent, respectively; BKZ/BKZ: 75.4 percent and 68.8%). Among the 44 UST/BKZ Week 52 PASI90 non-responders, high levels of response were rapidly achieved after switching to BKZ, with 77.3 percent achieving PASI90 and 40.9 percent achieving PASI100 at Week 56 after just one BKZ dose. Response was sustained and further improved at Week 100, with 84.1 percent and 54.5 percent achieving PASI90 and PASI100, respectively. Through Weeks 52–100 incidences of serious treatment emergent adverse events (TEAEs) were 7.4 percent in UST/BKZ switchers and 7.2 percent with BKZ/BKZ. One BKZ/BKZ death occurred which was not considered treatment-related. The most common TEAEs in the OLE were nasopharyngitis (UST/BKZ: 22.8%; BKZ/BKZ: 21.7%), oral candidiasis (13.2%; 15.6%), and upper respiratory tract infection (8.8%; 6.5%). In both treatment groups, oral candidiasis cases were all mild or moderate and none led to discontinuation.

Conclusion: After switching to BKZ treatment in the OLE, response rates in UST/BKZ switchers were improved and, after 16 weeks, were comparable to patients who received continuous BKZ. Furthermore, UST/BKZ Week 52 PASI90 non responders showed substantial, rapid, and sustained improvements upon switching to BKZ. There were no unexpected safety findings in UST/BKZ switchers during the first year of the OLE.

Funding: Medical writing support provided by Costello Medical.

Disclosures: CL: Speaker (honoraria) for AbbVie, Celgene, Eli Lilly and Novartis; served as an investigator for AbbVie, Actavis, Amgen, Boehringer Ingelheim, Celgene, Coherus, CorEvitas, Dermira, Eli Lilly, Galderma, Glenmark, Janssen, LEO Pharma, Merck (MSD), Novartis, Novella, Pfizer, Sandoz, Stiefel and Wyeth; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Dermira, Eli Lilly, Janssen, LEO Pharma, Pfizer, Sandoz, UCB Pharma and Vitae.

PGS: Has been an advisor and/or received speaker honoraria or travel expense reimbursements and/or received grants and/or participated in clinical trials for AbbVie, Actelion, ALK, Almirall, Amgen, Celgene, Eli Lilly, Galderma Abbott, Gilead, Janssen, LEO Pharma, Merck (MSD), Maruho, Novartis and UCB.

AM: Received research grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio and UCB Pharma.

GK: Received travel grants or honoraria or has been a consultant member of advisory boards and speaker’s bureaus or has served as investigator for AbbVie, Actelion, Basilea, Biogen, Celgene, Hexal-Sandoz, Janssen, LEO Pharma, Eli Lilly, Merck (MSD), Novartis, Pfizer and UCB Pharma. 

AB: Served as a scientific adviser and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma and UCB Pharma.

RBW: Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis and UCB Pharma; honoraria from Astellas, DiCE, GSK and Union. 

DDC, CM, VV, MW: Employees and shareholders of UCB Pharma.  

KAP: Received honoraria and/or grants from AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Canfite, Celgene, Coherus, Dermira, Dice Pharmaceuticals, Dow Pharma, Eli Lilly, Evelo, Galapagos, Galderma, Genentech, Gilead, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, MedImmune, Merck (MSD), Merck-Serono, Mitsubishi Tanabe Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB Pharma and Valeant/Bausch Health. 

 

Bimekizumab versus secukinumab in plaque psoriasis: higher efficacy translates into benefits in patient-perceived symptoms and health-related quality of life in the BE RADIANT multicenter, Randomized, Double-blinded Phase 3b Trial

Presenters: Augustin M,1 Gottlieb AB,2 Laws P,3 Wu JJ,4 Sebastian M,5 Eusebi P,6 Gomez NN,6 Vermeersch S,6 Cioffi C,7 Ciaravino V,8 Gordon KB9

Affiliations: 1Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; 2Icahn School of Medicine at Mount Sinai, New York, New York; 3Leeds Teaching Hospital, Leeds, UK; 4Dermatology Research and Education Foundation, Irvine, California; 5Mahlow Dermatology Practice, Blankenfelde-Mahlow, Germany; 6UCB Pharma, Brussels, Belgium; 7UCB Pharma, Raleigh, North Carolina; 8UCB Pharma, Colombes, France; 9Medical College of Wisconsin, Milwaukee, Wisconsin.

Background: Plaque psoriasis is a chronic, immune-mediated disease which can have a profound impact on individuals’ health-related quality of life (HRQoL).1 The Psoriasis Symptoms and Impacts Measure (P-SIM) is a novel, validated, patient-reported outcome tool developed to capture key signs, symptoms and life impacts of psoriasis.2 We examine how achievement of absolute Psoriasis Area and Severity Index (PASI) thresholds translates to improvements in P-SIM scores and Dermatology Life Quality Index (DLQI) in patients with moderate to severe plaque psoriasis receiving bimekizumab (BKZ) vs secukinumab (SEC).

Methods: In the BE RADIANT Phase 3b, double-blinded, active comparator-controlled trial (NCT03536884), patients were randomized 1:1 to BKZ 320mg every four weeks (Q4W) or SEC 300mg weekly to Week 4 then Q4W.3 At Week 16, BKZ-treated patients were re-randomized to BKZ 320mg Q4W or every eight weeks (Q8W) maintenance dosing. PASI=0 indicated complete skin clearance; PASI≤2 indicated disease control.4 The itching, skin pain and scaling items of the P-SIM were selected for analysis due to their clinical relevance and importance to patient experience. P-SIM score of 0/DLQI score of 0 or 1 indicated no patient-reported symptoms/impact on HRQoL. Patients achieving PASI=0 or PASI≤2 and DLQI0/1 or a P‑SIM score of 0 in each item at Wk16 and Wk48 are reported (observed case). Week 16 data are for the intention-to-treat population. Data reported at Week 48 are for the maintenance set (all patients who received ≥1 dose of study treatment at Week 16 or later).

Results: At Week 0, 373 patients were randomized to BKZ Q4W and 370 to SEC. From Week 16, patients received BKZ Q4W (N=147), BKZ Q8W (N=215) and SEC (N=354). A greater proportion of BKZ- vs SEC-treated patients achieved PASI=0 (64.1% vs 51.1%) and PASI≤2 (88.6% vs 79.9%) at Week 16; this was maintained through to Week 48 irrespective of Q4W or Q8W BKZ dosing. 

Across all treatment arms, higher disease control rates translated to greater clearance rate of patient-perceived symptoms and HRQoL impact. At Week 48, 62.5 percent (Q4W/Q4W) and 67.8 percent (Q4W/Q8W) achieved PASI≤2 and a P-SIM itching score of 0 for BKZ vs 53.8 percent for SEC; 80.9 percent (Q4W/Q4W) and 85.9 percent (Q4W/Q8W) achieved PASI≤2 and a score of 0 in the P-SIM skin pain item for BKZ vs 73.6 percent for SEC; 76.5 percent (Q4W/Q4W) and 77.4 percent (Q4W/Q8W) achieved PASI≤2 and a score of 0 in the P-SIM scaling item for BKZ vs 56.3 percent for SEC. 83.1 percent (Q4W/Q4W) and 83.4 percent (Q4W/Q8W) achieved PASI≤2 and DLQI0/1 for BKZ vs 74.8 percent for SEC.

Conclusion: More patients treated with BKZ achieved higher levels of disease control and lasting complete skin clearance at Week 16 and Week 48 vs SEC. This translated into greater resolution of patient-perceived symptoms and benefits in HRQoL; more BKZ-treated patients simultaneously achieved PASI=0 or PASI≤2 and DLQI0/1 or P-SIM scores of 0 for itching, skin pain and scaling at Week 48.

Funding: Funding was provided by UCB Pharma. Medical writing support provided by Costello Medical.

Disclosures: MA: Consulting fees from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, GSK, Hexal, Janssen, LEO Pharma, Medac, Merck, MSD, Mundipharma, Novartis, Pfizer, Sandoz, UCB Pharma and Xenoport.

ABG: Honoraria as an advisory board member and consultant for Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharma, UCB Pharma, and XBiotech (only stock options); research/educational grants (paid to Mount Sinai Medical School) from Boehringer Ingelheim, Incyte, Janssen, Novartis, Sun Pharma, UCB Pharma, and XBiotech.

PL: Honoraria and/or grants as an investigator, speaker, and/or advisory board member for AbbVie, Actelion, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Sanofi and UCB Pharma. 

JJW: Investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharma, UCB Pharma, Valeant Pharmaceuticals North America LLC, and Zerigo Health.

MS: Received honoraria as an investigator, or received grants and has been an advisor/consultant for: AbbVie, Affibody, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Dr. August Wolff, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Genentech, GSK, Incythe, Janssen, LEO Pharma, MedImmune, MSD, Mundipharma, Novartis, Pfizer, Regeneron, and UCB Pharma.

PE, NNG, SV, VC: Employees of UCB Pharma.

CC: Employee and shareholder of UCB Pharma.

KBG: Consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma; research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis and UCB Pharma.

JGK has grants paid to institution from AbbVie, Akros, Allergan, Amgen, Avillion, Biogen MA, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Eli Lilly, Exicure, Incyte, Innovaderm, Janssen, LEO Pharma, Novan, Novartis, Paraxel, Pfizer, Regeneron, Sienna, UCB Pharma and Vitae; personal fees from AbbVie, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigne, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Escalier, LEO Pharma, Nimbus, Novartis, Menlo, Pfizer, Sanofi, Sienna, Sun Pharma, UCB Pharma and Valeant.

NM is an honoraria, advisor, and/or paid speaker for and/or participated as principal investigator in clinical trials for AbbVie, Almirall, Asana, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene Corporation, Dermira, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Genentech, Incyte, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma and UCB Pharma.

RV is a consultant, and/or scientific advisor, and/or investigator, and/or speaker for AbbVie, Amgen, Astellas, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck (MSD), Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda and UCB Pharma.

DPT is an investigator and/or speaker for AbbVie, Amgen, Arcutis, Avillion, Bausch Health, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Merck-Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Sun Pharma and UCB Pharma.

DT has honoraria for participation on advisory boards, as a speaker and for consultancy from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS-Biopharma, Eli Lilly, Galapagos, Janssen, LEO Pharma, Morphosis, Novartis, Pfizer, Regeneron, Samsung, Sandoz-Hexal, Sanofi and UCB Pharma; Research grants received from Celgene and Novartis. 

MW is an employee of UCB Pharma. CC and CM are employees and shareholders of UCB Pharma.

RBW has research grants from AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer and UCB Pharma; Consultant for AbbVie, Almirall, Amgen, Arena, Avillion, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma.

 

Certolizumab pegol three-year durability of efficacy for moderate to severe plaque psoriasis in different subgroups: CIMPASI-1 and CIMPASI-2

Presenters: Thaçi D,1 Poulin Y,2 Gottlieb AB,3 Leonardi C,4 Pousa ID,5 Tilt N,6 Fierens F,7 Blauvelt A,8 

Affiliations: 1Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 2Centre de Recherche Dermatologique du Québec Métropolitain, Québec, Canada; 3Dept. of Dermatology; The Icahn School of Medicine at Mt Sinai, New York; 4Central Dermatology and Saint Louis University School of Medicine, St. Louis, Missouri; 5UCB Pharma, SA, Spain; 6UCB Pharma, Slough, UK; 7UCB Pharma, Brussels, Belgium; 8Oregon Medical Research Center, Portland, Oregon

Background: Certolizumab pegol (CZP), the Fc-free, PEGylated, anti-tumor necrosis factor medication, confers clinical benefits to plaque psoriasis (PSO) patients over 144 weeks of treatment in Phase 3 trials.1,2 Here, we present the durability of CZP efficacy after three years of treatment in subgroups of male and female patients based on baseline demographics and disease characteristics. 

Methods: Data were pooled from the CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) Phase 3 trials (study designs reported previously).2 For double blinded treatment, adults with PSO for ≥6 months were randomized 2:2:1 to CZP 200mg every two weeks (Q2W) (CZP 400mg at Weeks 0/2/4), 400mg Q2W, or placebo. Patients completing double-blinded treatment to Week 48 and achieving a ≥50% improvement from baseline in PASI (PASI50) entered the open-label phase, receiving CZP 200mg Q2W with subsequent PASI response-based dosing adjustment permitted. Responder rates were based on a logistic regression model. Non-responder imputation was used for patients not achieving a PASI50 response at Week 16 (escape arm entry criterion) or at Week 32 onwards (mandatory withdrawal); the Markov Chain Monte Carlo method for multiple imputation was used for other missing data. Patients were subcategorized based on baseline demographics and disease characteristics and data from patients randomized to 200mg CZP Q2W and 400mg CZP Q2W were pooled for males and females in each group. Here, we report the proportion of male and female patients randomized to receive CZP in various subgroups who achieved PASI90 at Week 144.

Results: At Week 0, 228 males and 133 females were randomized to receive either CZP 200mg Q2W or 400mg Q2W. Baseline characteristics were similar between groups; for males and females, mean age was 45.3/45.4, mean PASI was 20.0/18.4, and mean disease duration (years) was 16.6/20.7, respectively. 

Overall, PASI90 response rates at Week 144 were 47.8 percent among male patients and 47.7 percent among female patients. Numerically higher PASI90 response rates were observed for those aged 18–<45 years, compared with those aged 45 and over, and for those without prior use of biologics, compared with patients who had used biologics before CZP treatment. These numerical differences in PASI90 responses based on age and prior use of biologics were greater for females than males. PASI90 was achieved by numerically higher proportions of patients with a body mass index (BMI) of <35 at Week 144, compared to patients with a BMI of ≥35. CZP efficacy was observed in patients with various disease durations and baseline PASIs. Regardless of baseline PASI, over 42 percent of males and females achieved PASI90 at Week 144 of treatment with CZP. The PASI90 response rate was largely consistent across disease durations in males and was not negatively affected by longer disease duration in females.  

Conclusion: Long-term CZP treatment conferred clinical efficacy in both male and female patients with different demographics and disease characteristics, although some numerical differences in PASI90 responses were observed. 

Funding: Funding was provided by UCB Pharma. Medical writing support was provided by Costello Medical.

Disclosures: DT: Honoraria for participation on advisory boards, as a speaker and for consultancy for AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS Biopharma, Eli Lilly, Galapagos, Janssen, LEO Pharma, Morphosis, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi Genzyme and UCB Pharma; research grants received from Celgene, LEO Pharma and Novartis.

YP: Investigator (research grants) for AbbVie, Baxter, Boehringer Ingelheim, Celgene, Centocor/Janssen, Eli Lilly, EMD Serono, GSK, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Takeda and UCB Pharma; speaker (honoraria) for AbbVie, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Regeneron and Sanofi Genzyme.

ABG: Honoraria as an advisory board member and consultant for Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharma, UCB Pharma and XBiotech (only stock options); research/educational grants (paid to Mount Sinai Medical School) from Boehringer Ingelheim, Incyte, Janssen, Novartis, Sun Pharma, UCB Pharma and XBiotech.

CL: Speaker (honoraria) for AbbVie, Celgene, Eli Lilly and Novartis; served as an investigator for AbbVie, Actavis, Amgen, Boehringer Ingelheim, Celgene, Coherus, Corrona, Dermira, Eli Lilly, Galderma, Glenmark, Janssen, LEO Pharma, Merck (MSD), Novartis, Novella, Pfizer, Sandoz, Stiefel and Wyeth; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Dermira, Eli Lilly, Janssen, LEO Pharma, Pfizer, Sandoz, UCB Pharma and Vitae. Treasurer of the International Psoriasis Council Fellow of the American Academy of Dermatology Member of the American Dermatological Association Adjunct Professor of Dermatology at St. Louis University School of Medicine. Private practice in St. Louis, MO.

IDP, FF: Employee of UCB Pharma

NT: Employee and stockholder of UCB Pharma

AB: Scientific adviser and/or investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma and UCB Pharma.

 

Combined analysis of two head-to-head Phase 3 trials demonstrating superior improvement of patient reported outcomes for calcipotriene and betamethasone dipropionate cream compared to gel/topical suspension in treatment of plaque psoriasis

Presenters: Armstrong A,1 Præstegaard M,2 Selmer J,2 Reich A,3 Pinter A,4

Affiliations: 1Keck School of Medicine, Department of Dermatology, University of Southern California Los Angeles; 2MC2 Therapeutics, Hørsholm, Denmark; 3Medical College of Rzeszow; University, Dept. of Dermatology, Rzeszów, Poland; 4University Hospital Frankfurt am Main, Dept. of Dermatology, Frankfurt am Main, Germany

Background: Calcipotriene and betamethasone dipropionate (0.005%/0.064% w/w) cream (CAL/BDP cream) is based on PAD Technology enabling development of an easy to apply water-containing cream of CAL and BDP, despite their known pH-related instability when combined in the presence of water. The objective of this analysis is to analyze the combined patient reported outcomes data from two Phase 3 studies conducted in the US and EU.

Methods: CAL/BDP cream was evaluated in two head-to-head, Phase 3, randomized, multicenter, investigator-blind, parallel-group trials comparing the efficacy and safety of CAL/BDP cream to vehicle and an active comparator (0.005%/0.064% w/w CAL/BDP gel/topical suspension (TS)) in adults with plaque psoriasis. Eligible patients were adults with a diagnosis of plaque psoriasis involving the trunk and/or limbs. Additional key inclusion criteria included a treatment area involving between 2% and 30 percent of the body surface area and a physician global assessment (PGA) score of mild or moderate disease severity. Patients were instructed to apply the treatment topically once daily to affected areas for up to eight weeks. Statistical analyses were based on a modified intention-to-treat population (n=1271), which included all randomized patients with at least one assessment of PGA after starting treatment.

Results: The PGA treatment success was significantly greater for CAL/BDP cream (43.2%) than for CAL/BDP Gel/TS (31.9%) at Week 8 (p<0.0001). Similarly, the proportion of patients evaluating their treatment to have improved by at least two grades to clear or very mild disease (defined as the Subject Global Assessment (SGA) success) was significantly higher in the CAL/BDP cream group as compared to the CAL/BDP gel/TS group (Week 8, 44.2% vs 27.9%, p<0.0001). A DLQI score of 0 or 1 (i.e. the psoriasis disease did not affect the patient’s life) at Week 8 was obtained by 43.8% in the CAL/BDP cream group and 34.2% in the CAL/BDP gel/TS group (p=0.0005). A significantly higher proportion of patients achieved a clinically important improvement of at least 4-points in DLQI for CAL/BDP cream (>60% of patients from Week 4) compared to CAL/BDP gel/TS. Treatment convenience of CAL/BDP cream, as measured by the Psoriasis Treatment Convenience Scale, was superior to the CAL/BDP gel/TS at all studied time points, including questions addressing greasiness of the formulation and overall satisfaction of treatment.

Conclusion: CAL/BDP cream is a novel topical treatment for psoriasis, which through PAD™ Technology offers excellent QoL and treatment satisfaction for patients. Given these data CAL/BDP cream may lead to better adherence to treatment which ultimately may result in better treatment outcomes in clinical practice.

Funding: Trial funded by MC2 Therapeutics.

 

Comparative effectiveness of guselkumab in psoriatic arthritis: Updates to a systematic literature review and network meta-analysis

Presenters: Mease JP,1 McInnes IB,2 Tam L,3 Rajalingam R,4 Peterson S,5 Hassan F6, Chakravarty SD,7 Contr C,8 Armstrong A4, Wolf-Henning Boehncke W,9 Ritchlin C10

Affiliations: 1Swedish Medical Center/Providence St. Joseph Health & University of Washington, Seattle, WA; 2University of Glasgow, Glasgow, United Kingdom; 3The Chinese University of Hong Kong and The Prince of Wales Hospital, Department of Medicine & Therapeutics, Hong Kong; 4EVERSANA, Burlington, Ontario, Canada; 5Janssen Global Services, Horsham, PA; 6Janssen EMEA, High Wycombe, England; 7Janssen Scientific Affairs, LLC, Horsham, PA & Drexel University College of Medicine, Philadelphia, PA; 8Janssen Pharmaceuticals Companies of Johnson & Johnson, Issy-les-Moulneaux, France; 9Geneva University Hospitals, Geneva, Switzerland; 10University of Rochester, Rochester, NY

Background: The efficacy of the interleukin (IL)-23 p19-subunit inhibitor guselkumab (GUS) for psoriatic arthritis (PsA) has been demonstrated in two pivotal Phase 3 trials (DISCOVER‑1 & -2). A third Phase 3b trial, COSMOS, evaluated GUS in patients with PsA who had an inadequate response (IR) to tumor necrosis factor inhibitors (TNFi). GUS has previously been compared to targeted PsA therapies through network meta-analysis (NMA). The objective of this NMA update was to include data for GUS in TNFi-IR patients from COSMOS, as well as two additional key comparators, risankizumab (RIS), an IL-23 inhibitor and upadacitinib (UPA), a Janus kinase inhibitor (JAKi).

Methods: A systematic literature review identified PsA randomized controlled trials up to February 2021. A subsequent hand-search identified data for newer agents, including congresses up to July 2021. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs). Analyses used fixed or random effects models and adjusted for placebo response via meta-regression on baseline risk when feasible; multinomial models were used for ACR and PASI. Results are summarized by ranking treatments in league tables according to results derived from NMAs. Conclusions (ie, comparable or better/worse) for GUS 100mg every eight weeks (Q8W) or four weeks (Q4W) versus comparators are based on overlap of pairwise 95 percent credible intervals (CrIs) (ie, treatments are comparable if CrIs overlap 1 [dichotomous outcomes] or 0 [continuous outcomes]).

Results: Thirty-three Phase 3 studies were included in the NMAs. Studies were placebo-controlled up to 24 weeks except for two head-to-head studies, and evaluated 15 targeted PsA therapies in TNFi naïve, IR, or mixed populations. For ACR 20 response, GUS Q8W and Q4W ranked 14th and 12th among 23 treatments and were comparable to most other active agents, including RIS and UPA, subcutaneous (SC) TNFi, and most IL-17A inhibitors (IL-17Ai), as demonstrated by overlap in pairwise 95% CrIs with unity. Results were similar for ACR 50 and 70 responses. For PASI 90, GUS Q8W and Q4W ranked 2nd and 1st among 23 treatments and were better than multiple agents, including all SC TNFi, JAKi, including UPA, and other small molecules, as demonstrated by nonoverlap in pairwise 95 percent Crls with unity. GUS Q8W and Q4W were similar to RIS and most IL-17Ai for PASI 90, but point estimates consistently favored GUS. For vdH-S score, GUS Q8W and Q4W ranked 8th and 3rd among 18 treatments; GUS Q4W was better than RIS, and both GUS Q8W and Q4W were comparable to most other agents, including UPA. SAEs were comparable across most agents.

Conclusion: GUS demonstrates better skin efficacy than most other targeted PsA therapies, including UPA. For vdH-S, both GUS dose regimens are comparable to most treatments, with both GUS dose regimens ranking higher than most, including UPA and RIS. Both GUS dose regimens demonstrate ACR responses that are comparable to most other agents, including UPA and RIS, and rank favorably in the network for SAEs.

Funding: This project was fully funded by Janssen Pharmaceuticals.

Disclosures: PJM consultancies: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB, Crescendo Bioscience; member of speakers’ bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Leo, Merck, Novartis, Pfizer, UCB, Crescendo Bioscience; grants/research support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB, Crescendo Bioscience; IBM consultancies: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, UCB; honoraria: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, UCB; grants/research support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB; L-ST consultancies: Janssen, Pfizer, Sanofi, AbbVie, Boehringer Ingelheim, Lilly; grant/research support: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis and Pfizer.; W-HB support from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, UCB; CR consultancies: AbbVie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, UCB; grants/research support: AbbVie, Amgen, Janssen, UCB; SP, FH, and CC are employees of Janssen Pharmaceuticals and shareholders of Johnson & Johnson; SDC is an employee of Janssen Scientific Affairs, LLC, and shareholder of Johnson & Johnson; RR and AA are employees of EVERSANA, received consultancy fees from Janssen Pharmaceuticals for this project.

 

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, compared with placebo and apremilast in moderate to severe plaque psoriasis: integrated laboratory parameter results from the Phase 3 POETYK PSO-1 and PSO-2 trials

Presenters: Thaçi D,1 Gordon KB,2 Gooderham M,3 Strober B,4 Korman NJ,5 Banerjee S,6 Colston E,6 Kim J,6 Throup J,6 Akimichi Morita7

Affiliations: 1University of Lübeck, Lübeck, Germany; 2Medical College of Wisconsin, Milwaukee, WI; 3SKiN Center for Dermatology, Queen’s University, and Probity Medical Research, Waterloo, ON, Canada; 4Yale University, New Haven, CT, and Central Connecticut Dermatology, Cromwell, CT; 5Case Western Reserve University and University Hospitals, Cleveland, OH; 6Bristol Myers Squibb, Princeton, NJ; 7Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Background: Deucravacitinib, an oral, selective TYK2 inhibitor, binds to the regulatory domain and inhibits TYK2 via an allosteric mechanism distinct from Janus kinase inhibitors that bind to the conserved active site in the kinase domain. In the Phase 3 POETYK PSO-1 and PSO-2 trials, deucravacitinib was significantly more efficacious than placebo or apremilast and well tolerated in patients with moderate to severe plaque psoriasis. This analysis used integrated data from both trials to compare the effects of deucravacitinib versus placebo and apremilast on laboratory parameters.

Methods: The double-blind, 52-week POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials randomized patients with moderate to severe plaque psoriasis (body surface area ≥10%, Psoriasis Area and Severity Index [PASI] ≥12, static Physician’s Global Assessment ≥3) 2:1:1 deucravacitinib 6mg once daily, placebo, or apremilast 30mg twice daily. Patients receiving placebo were switched to deucravacitinib at Week 16; patients receiving apremilast who failed to meet trial-specific efficacy thresholds (PSO-1: PASI 50; PSO-2: PASI 75) were switched to deucravacitinib at Week 24. Changes from baseline levels of lymphocytes, neutrophils, platelets, hemoglobin, total cholesterol, triglycerides, creatine phosphokinase (CPK), creatinine, ALT, and AST were evaluated. Shifts in Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) severity grade of laboratory parameter abnormalities between baseline and Week 16 were assessed. Integrated data from PSO-1 and PSO-2 are presented.

Results: A total of 666 and 1020 patients were randomized in PSO-1 and PSO-2, respectively, and included in this analysis. Overall, no clinically meaningful changes from baseline levels were observed in any laboratory parameter over the placebo-controlled period (Weeks 0–16). Grade ≥3 laboratory abnormalities occurred at low frequencies and were comparable across treatment groups through Week 16; shifts of ≥2 CTCAE grades from baseline were balanced overall and infrequent in all treatment groups. Triglyceride and CPK elevations were low and similar across treatment arms (<1.8%). No clinically relevant cumulative trends in laboratory parameters were observed up to Week 52 in patients randomized to deucravacitinib at baseline in PSO-1 who continued to receive deucravacitinib over 52 weeks. 

Conclusion: Deucravacitinib did not result in clinically significant laboratory parameter abnormalities in two large Phase 3 trials in psoriasis, suggesting routine laboratory monitoring during deucravacitinib treatment may not be warranted.

Funding: This clinical trial was sponsored by Bristol Myers Squibb. Writing and editorial assistance were provided by Lisa Feder, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, funded by Bristol Myers Squibb.

Disclosures: DT: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB

KBG: Grant support and consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB; Consulting fees: Amgen, Almirall, Dermira, Leo Pharma, Pfizer, and Sun Pharma

MG: Advisory board, principal investigator, and lecture fees: AbbVie, Galderma, Leo Pharma, Pfizer, and Regeneron; Advisory board and lecture fees: Actelion; Principal investigator and consulting fees: Akros Pharma; Advisory board, principal investigator, lecture fees, and consulting fees: Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Sanofi Genzyme, and Valeant; Principal investigator: Arcutis, Bristol Myers Squibb, Dermira, GlaxoSmithKline, MedImmune, Merck, Roche Laboratories, and UCB; Principal investigator and lecture fees: Glenmark

BS: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, Equillium, GlaxoSmithKline, Janssen, Immunic Therapeutics, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, Ortho Dermatologics, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Ventyxbio; Speaker: AbbVie, Janssen, Lilly, and Sanofi Genzyme; Scientific co-director (consulting fee): CorEvitas’ (Corrona) Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas’ (Corrona) Psoriasis Registry, Dermavant, Eli Lilly/Dermira, and Novartis

NJK: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB; Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech. Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi Genzyme

SB, EC, JK, and JT: Employees and shareholders: Bristol Myers Squibb.

AM: Grant/research support, consultant, speakers bureau: AbbVie, Boehringer Ingelheim,Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, Leo Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB, and Ushio

 

Differences in patient and dermatologist perspectives on psoriasis treatment: Results from the UPLIFT survey

Presenters: Reich K,1 Gisondi P,2 Gold LS,3 Peter Kerkhof P,4 Langley R,5 Paul C,6 Puig L,7 Hideshi T,8 Richter S,9 Jardon S,9 Tang L,9 Lebwohl M10

Affiliations: 1University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2University Hospital of Verona, Verona, Italy; 3Henry Ford Health System, West Bloomfield, MI; 4Radboud University Medical Center, Nijmegan, Netherlands; 5Dalhousie University, Halifax, Nova Scotia, Canada; 6Paul Sabatier University, Toulouse, France; 7Hospital de la Santa Creu I Sant Pau, Barcelona, Spain; 8Tokyo Yamate Medical Center, Tokyo, Japan; 9Amgen Inc., Thousand Oaks, CA; 10Icahn School of Medicine at Mount Sinai, New York, NY

Background: The Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey, conducted in 2020, assessed patient and physician relationships and perceptions regarding disease burden and treatment of psoriatic disease. Patient and disease characteristics, including psoriasis (PsO) symptoms, body surface area (BSA) involvement, perceived severity, and disease burden from UPLIFT have been previously reported. Here we describe patient and dermatologist perspectives on factors contributing to disease severity and expectations for PsO treatment and explore how well patient and physician perspectives align.

Methods: UPLIFT involved multinational web-based surveys administered to dermatologists and adults with self-reported, healthcare professional–diagnosed PsO conducted from March 2 to June 3, 2020, in eight countries (United States, Canada, United Kingdom, France, Germany, Italy, Spain, and Japan). Patient and physician alignment on determinants of disease severity, treatment priorities, and treatment goals was assessed. Respondents were asked to rank their top three contributing factors for each metric. Results were analyzed using the sum of scores. 

Results: A total of 3,806 patients and 473 dermatologists completed the respective surveys; 2,550 patients reported healthcare professional–diagnosed PsO, without psoriatic arthritis. Most patients (56%) reported limited skin involvement (BSA ≤3%). Of dermatologists surveyed, nearly half (48.6%) practiced in a community/office-based setting. With respect to disease burden, patients ranked type of symptoms, length of time suffering from PsO, and location of skin lesions as the top three most important factors defining disease severity. In contrast, physicians ranked impact on overall quality of life, amount of BSA involvement, and type of symptoms as the top three factors; disease duration was ranked no. 10 and location of lesions no. 4. Concerning the treatment of psoriasis, reducing itching was the top treatment goal for patients, followed by keeping their symptoms controlled and skin clearance. Physicians, however, rated itch reduction as a less important goal for treatment and ranked improving quality of life as the most important goal. Regarding treatment goals, patients and physicians thought that their goals were very closely or somewhat closely aligned and that there was a moderate to strong need for better therapies for PsO. Similar responses regarding top attributes of an ideal PsO therapy (i.e., skin clearance and long-term efficacy) were observed between patients and physicians, with long-term safety an additional focus for physicians. When asked about what occurs at office visits, patient and physician recall differed markedly, with considerably more patients than physicians reporting never discussing things like joint damage (39.3% vs 1.7%), related conditions (39.3% vs 3.2%), and impact of PsO on emotional well-being (34.0% vs 4.7%).

Conclusion: In the 2020 UPLIFT survey, differences between patient and physician perspectives about PsO burden and treatment were observed. There was a greater patient focus on specific symptoms of PsO, whereas physicians placed greater importance on overall quality of life. Furthermore, recall of past office visits differed between patients and physicians, highlighting an opportunity for patient and physician dialogue to improve with respect to PsO treatment and goals of therapy. 

Funding: This study was sponsored by Amgen, Inc. Writing support was funded by Amgen and provided by Kristin Carlin, BSPharm, MBA, of Peloton Advantage, LLC, an OPEN Health company, and Cathryn M. Carter, MS, employee of and stockholder in Amgen Inc.

Disclosures: KR: AbbVie, Affibody, Almirall, Amgen Inc., Avillion, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Covagen, Dermira, Eli Lilly, Forward Pharma, Fresenius Medical Care, Galapagos, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Medac, Merck Sharp & Dohme, Novartis, Miltenyi Biotec, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB, Valeant, and Xenoport – paid speaker and/or participated in clinical trials.

PG: AbbVie, Amgen Inc., Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB – consultant and grant/research support.

LSG: AbbVie, Amgen, Arcutis, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant – honoraria, grants, and/or research funding as a speaker, investigator, and/or advisory board member.

PvdK: AbbVie, Almirall, Bristol-Myers Squibb, Celgene, Dermavant, Eli Lilly, Janssen, LEO Pharma, and Novartis – consultant and/or lecturer.

RGL: AbbVie, Amgen Inc., Boehringer Ingelheim, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, and UCB – principal investigator, scientific advisory board, or speaker.

CP: AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Pfizer, Pierre Fabre, Sanofi, and UCB – research support; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Pierre Fabre, Pfizer, Regeneron, Sanofi, and UCB – honoraria/consultant.

LP: AbbVie, Amgen Inc., Boehringer Ingelheim, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB – fees; AbbVie, Almirall, Amgen Inc., Baxalta, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Gebro, Janssen, LEO Pharma, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB – honoraria and consultant fees; Celgene, Eli Lilly, Janssen, MSD, Novartis, and Pfizer – company-sponsored speakers bureaus.

HT: AbbVie, Celgene, Eli Lilly, Janssen, Kyowa Kirin, and Novartis – honoraria and consultant fees.

SR, SJ, & LT: Amgen Inc. – employment.

ML: Mount Sinai – employment; AbbVie, Amgen Inc., Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen, LEO Pharma, Ortho Dermatologics, Pfizer, and UCB – research funds; Aditum Bio, Allergan, Almirall, Arcutis, Avotres Therapeutics, BirchBioMed, BMD Skincare, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Serono, Theravance, and Verrica – consultant.

 

Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPSaKE 1

Presenters: Kristensen LE,1 Keiserman M,2 Papp K,3 McCasland L,4 White D,5 Lu W,6 Soliman AM,6 Eldred A,6 Barcomb L,6 Behrens F,7

Affiliations: 1The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark; 2Rheumatology Section, Pontifical Catholic University, School of Medicine, Porto Alegre, Brazil; 3Probity Medical Research–K Papp Clinical Research, Waterloo, Ontario, Canada; 4Department of Rheumatology, Loyola University Medical Center, Maywood, Illinois, United States; 5Rheumatology Department, Waikato Hospital, Hamilton, New Zealand; 6AbbVie Inc., North Chicago, Illinois, United States; 7Rheumatology University Hospital and Fraunhofer Institute for Translational Medicine and Pharmacology ITMP Goethe-University Frankfurt, Germany

Background: RZB, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits the p19 subunit of the human cytokine IL-23, is being investigated as a treatment for PsA.

Methods: KEEPsAKE 1 (NCT03675308) is an ongoing, Phase 3 study that includes a screening period; a 24-week double-blinded, placebo-controlled, parallel-group period (period 1); and an open-label extension period (period 2). Eligible patients aged ≥18 years with active PsA (symptom onset ≥6 months prior to screening, meeting the Classification Criteria for PsA [CASPAR], and ≥5 swollen and ≥5 tender joints) and who had an inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR), were randomized 1:1 to receive RZB 150 mg or placebo (PBO) at Weeks 0, 4, and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology (ACR20) response at Week 24. Period 2 started at Week 24, and patients were switched to receive open-label RZB 150 mg every 12 weeks through Week 208. Mixed-effect model repeated measures and nonresponder imputation methods were used to assess continuous and binary variables, respectively. Efficacy and safety were analyzed in all patients who received ≥1 dose of study drug through Week 52. Treatment-emergent adverse events (TEAE) were summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [PY]).

Results: At Week 24, 51.3 percent of RZB-treated (N=224) and 26.5% of PBO-treated (N=219) patients achieved ACR20. At Week 52, 58.5 percent of patients who were randomized to RZB and 55.7 percent of patients who were randomized to PBO and then switched to RZB at week 24 achieved ACR20. In patients with ≥3% of body surface area affected at baseline, 55.0 percent of RZB-treated patients (N=123) and 10.2 percent of PBO-treated patients (N=119) achieved PASI 90 at Week 24. At Week 52, 64.2 percent of patients randomized to RZB and 59.7 percent of patients who were randomized to PBO and then switched to RZB at Week 24 achieved PASI 90. For other efficacy measures, similar trends were observed. RZB was well tolerated through 52 weeks of treatment, and EAERs of adverse events were stable between Weeks 24 and 52. At the Week 52 data cutoff (19 April 2021), the total EAER of any TEAE in patients receiving RZB was 184.2/100 PY.

Conclusion: Continuous RZB treatment resulted in maintained efficacy responses with a consistent safety profile through 52 weeks of treatment in patients with active PsA who were Bio-IR and/or csDMARD-IR.

Funding: AbbVie Inc. funded the research for this study and provided writing support for this poster.

 

Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from KEEPSaKE 2

Presenters: Östör A,1 Van den Bosch F,2 Papp K,3 Asnal C,4 Blanco R,5 Aelion J,6 Lu W,7 Wang Z,7 Soliman AM,7 Eldred A,7 Padilla B,7 Kivitz A8

Affiliations: 1Monash University, Cabrini Hospital, Melbourne, Victoria, Australia; 2Department of Rheumatology, Ghent University, Ghent, Belgium; 3Probity Medical Research–K. Papp Clinical Research, Waterloo, Ontario, Canada; 4DOM Centro de Reumatología, Buenos Aires, Argentina; 5Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain; 6Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; 7AbbVie Inc., North Chicago, Illinois; 8Altoona Center for Clinical Research, Duncansville, Pennsylvania

Background: RZB, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits the p19 subunit of the human cytokine interleukin-23, is being investigated as a treatment for PsA.

Methods: KEEPsAKE 2 (NCT03671148) is an ongoing, Phase 3, multicenter study that includes a screening period; a 24-week double-blinded, randomized, placebo-controlled, parallel-group period (Period 1); and an open-label extension period (Period 2). Eligible patients were ≥18 years of age with active PsA (symptom onset ≥6 months before screening, meeting Classification Criteria for PsA [CASPAR], and ≥5 tender and ≥5 swollen joints) and had inadequate response or intolerance to 1 or 2 biologic therapies (Bio-IR) and/or ≥1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR). Patients received RZB 150mg or placebo (PBO) at weeks 0, 4, and 16 (1:1). The primary endpoint was the proportion of patients achieving ACR20 response at week 24. Period 2 started at Week 24, and patients were switched to receive open-label RZB 150 mg every 12 weeks through Week 208. Efficacy and safety were analyzed in patients who received ≥1 dose of study drug through Week 52. Mixed-effect model with repeated measures and nonresponder imputation methods were used to assess continuous and binary variables, respectively. Treatment-emergent adverse events (TEAEs) were summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [PY]).

Results: At Week 24, a greater proportion of RZB-treated (N=483) vs PBO-treated (N=481) patients achieved ACR20 (55.3% and 32.8%, respectively). At Week 52, 70 percent of patients who were randomized to receive RZB and 63 percent of patients who were randomized to receive PBO and switch to RZB at Week 24 achieved ACR20. In patients with ≥3% of body surface area affected at baseline, 52.7 percent of RZB-treated patients (N=273) and 9.9 percent of PBO-treated patients (N=272) achieved ≥90 percent improvement in Psoriasis Area and Severity Index (PASI 90) at Week 24; 67.8 percent who were randomized to receive RZB and 59.9 percent who were randomized to receive PBO and switch to RZB at Week 24 achieved PASI 90 at Week 52. Similar results were observed for other efficacy measures. RZB was well tolerated through 52 weeks of treatment. EAERs of adverse events were stable between weeks 24 and 52. At the Week 52 data cut-off (19 April 2021), the total EAER of any TEAE in patients receiving RZB was 143.1/100 PY.

Conclusion: Continuous RZB treatment provided durable efficacy and a consistent safety profile through 52 weeks of treatment in patients with active PsA who were csDMARD-IR.

Funding: AbbVie Inc. funded the research for this study and provided writing support for this poster.

 

Efficacy of certolizumab pegol in psoriasis patients failing to respond to etanercept: Three‑year results from the randomized Phase 3 CIMPACT trial 

Presenters: Pinter A,1 Blauvelt A,2 Fierens F,3 Tilt N,4 Arendt C,3 Sofen H5 

Affiliations: 1University Hospital Frankfurt, Frankfurt am Main, Germany; 2Oregon Medical Research Center, Portland, Oregon; 3UCB Pharma, Brussels, Belgium; 4UCB Pharma, Slough, UK; 5David Geffen School of Medicine at UCLA, Los Angeles, California

Background: Many patients with plaque psoriasis (PSO) do not respond to first-line biologic therapy and may be prescribed an alternative treatment. Therefore, it is important to understand how patients respond following treatment switch. Here, we assessed efficacy of certolizumab pegol (CZP) in patients failing to respond to etanercept (ETN).

Methods: The Phase 3 CIMPACT trial (NCT02346240) enrolled adult patients with moderate to severe PSO. Patients were randomized to CZP 200mg every two weeks (Q2W) (400mg loading dose Weeks 0/2/4), CZP 400mg Q2W, placebo, or ETN 50mg twice weekly for 12 weeks. Full study design has been reported previously.2 At Week 16, following a 4-week washout, inadequate responders to ETN (defined as patients not achieving ≥75% improvement from baseline Psoriasis Area and Severity Index [PASI75]) were eligible to enter an open label escape arm receiving CZP 400mg Q2W. Among ETN-randomized patients who were inadequate responders at Week 16, we report the proportions who achieved PASI75, PASI90, and PGA0/1 (Physician’s Global Assessment score of 0 or 1 [“clear” or “almost clear”] with ≥2-category improvement from baseline) to Week 144. Data are presented for all Week 16 ETN inadequate responders, and for subsets: ETN partial responders (≥PASI50, <PASI75), and ETN non-responders (<PASI50). Responder rates were based on a logistic regression model. Patients withdrawn due to lack of PASI50 response were treated as non-responders at subsequent timepoints; other missing data were imputed with multiple imputation using the Markov Chain Monte Carlo method.

Results: Of 170 patients randomized to ETN, 159 remained in the study at Week 16, of whom 82 failed to achieve PASI75 and entered the CZP 400mg Q2W escape arm (40 partial responders and 42 non­responders). 

At Week 48, following 32 weeks of CZP treatment, 85.3 percent of all ETN inadequate responders achieved PASI75, 61.9 percent achieved PASI90, and 73.9 percent achieved PGA0/1. At the same timepoint, among Week 16 ETN partial responders (≥PASI50, <PASI75), the PASI75, PASI90, and PGA0/1 responder rates were 92.6 percent, 63.4 percent, and 82.7 percent, respectively. Among Week 16 ETN non-responders (<PASI50), the PASI75, PASI90, and PGA0/1 responder rates were 77.4 percent, 57.9 percent, and 64.6 percent, respectively.

At Week 144, following 128 weeks of CZP treatment, 84.4 percent of all ETN inadequate responders achieved PASI75, 47.0 percent achieved PASI90, and 59.3 percent achieved PGA 0/1. At Week 144, among Week 16 ETN partial responders, the PASI75, PASI90 and PGA0/1 responder rates were 83.1 percent, 56.9 percent, and 73.9 percent, respectively. Among Week 16 ETN non-responders, the PASI75, PASI90, and PGA0/1 responder rates were 84.1 percent, 37.0 percent, and 44.6 percent, respectively.

Conclusion: Improvements were seen following switch from ETN to CZP 400mg Q2W, with over 75 percent of patients across ETN partial or non responders achieving PASI75 at Week 48, maintained to Week 144. Through Week 144, almost half of all ETN inadequate responders who switched to CZP achieved PASI90 and over half achieved PGA0/1, with higher durability of response observed among ETN partial responders. These data show that switching from ETN to CZP may be an appropriate treatment option for patients who do not respond to ETN. 

Funding: Funding was provided by Dermira Inc. and UCB Pharma.

Disclosures: AP: Investigator and/or speaker and/or advisor for AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi Pharma, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz, Schering-Plough, Tigercat Pharma, and UCB Pharma.

AB: Served as an scientific adviser and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Athenex, Boehringer Ingelheim, BMS, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma.

FF, CA: Employees of UCB Pharma.

NT: Employee and stockholder of UCB Pharma.

HS: Received consulting fees from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Janssen, Eli Lilly, Medimmune, Novartis, Pfizer, Sun Pharma, UCB Pharma, and Valeant.

 

Efficacy of spesolimab for the rapid control of generalized pustular psoriasis flares: results from the placebo-controlled Effisayil™ 1 study

Presenters: Bachelez H1,2, Barker J,3 Ghoreschi K,4 Elewski BE,5, Xu J,6 Hu N,7 Quaresma M,8 Thoma C,9 Lebwohl MG10

Affiliations: 1Service de Dermatologie, Assistance Publique-H pitaux de Paris H pital Saint-Louis, Paris, France; 2INSERM U1163, Imagine Institute for Genetics of Human Diseases, Universit de Paris, Paris, France; 3St John’s Institute of Dermatology, Guy’s Hospital, London, UK; 4Charit – Universit tsmedizin Berlin, Department of Dermatology, Venereology and Allergology, Berlin, Germany; 5University of Alabama at Birmingham, School of Medicine, Birmingham, AL; 6Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China; 7Boehringer Ingelheim (China) Investment Co., Ltd; 8Boehringer Ingelheim International GmbH, Ingelheim, Germany; 9Boehringer Ingelheim International GmbH, Biberach, Germany; 10Icahn School of Medicine at Mount Sinai, New York, NY

Background: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease characterized by recurrent flares of sterile, macroscopic pustules. GPP is an autoinflammatory condition, and the interleukin (IL)-36 pathway is central to its pathogenesis. Current treatments used to manage GPP flares have been reported to act too slowly in clearing pustules and associated symptoms. Here we report the efficacy of spesolimab from Effisayil 1, the first placebo-controlled study assessing a targeted therapy in patients with GPP flares, within one week of treatment.

Methods: Effisayil 1 (NCT03782792) is a multicenter, randomized, double-blind, placebo-controlled Phase 2 study in patients with a GPP flare. Patients with GPP flares (N=53) were randomly assigned 2:1 to a single 900 mg intravenous dose of spesolimab (n=35) or placebo (n=18) on Day 1 (baseline). Pustule and skin clearance were assessed using the GPP Physician Global Assessment (GPPGA) on Days 2, 3, and 8. The primary and key secondary endpoints were the proportions of patients achieving a GPPGA pustulation subscore of 0 (no visible pustules), and a GPPGA total score of 0 or 1 (clear/almost clear), on Day 8. Treatment effect at Day 8 was tested with a 1-sided alpha level of 0.025.

Results: On Day 2, a GPPGA pustulation subscore of 0 was achieved by 11.4 percent (4/35) of the spesolimab group compared with 0 patients in the placebo group. No patients achieved a GPPGA total score of 0 or 1. On Day 3, a GPPGA pustulation subscore of 0 was achieved by 31.4 percent (11/35) of patients in the spesolimab group compared with 0 patients in the placebo group. 5.7 percent (2/35) of patients in the spesolimab group achieved a GPPGA total score of 0 or 1 compared with 0 patients in the placebo group. On Day 8, a GPPGA pustulation subscore of 0 was achieved by 54.3 percent (19/35) of patients in the spesolimab group compared with 5.6 percent (1/18) of patients in the placebo group (p=0.0004). 42.9 percent (15/35) of patients in the spesolimab group achieved a GPPGA total score of 0 or 1 compared with 11.1 percent (2/18) of patients in the placebo group (p=0.0118).

Conclusion: In the Effisayil 1 study, spesolimab demonstrated superiority to placebo in terms of achievement of GPPGA pustulation subscore of 0 and GPPGA total score of 0 or 1 within 1 week. Furthermore, treatment of a GPP flare with spesolimab resulted in an improvement in pustulation as early as 24 hours following infusion. This analysis supports the efficacy of spesolimab in rapidly clearing pustules in patients presenting with GPP flares.

Funding: This study was funded by Boehringer Ingelheim.

 

Improvement in psoriasis symptoms and involvement in special areas: 32-week results from ADVANCE

Presenters: Gold LS,1 Papp K,2,3 Pariser D,4 Neal Bhatia N,5 Sofen H,6,7 Albrecht L,2,8,9 Gooderham M,2,10,11 Chen M,12 Paris M,12 Cheng S,12 Picard H,12 Wang Y,12 Green L13

Affiliations: 1Henry Ford Health System, West Bloomfield, MI; 2Probity Medical Research, Inc., Waterloo, ON, Canada; 3K Papp Clinical Research, Waterloo, ON, Canada; 4Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA; 5Therapeutics Clinical Research, San Diego, CA; 6UCLA School of Medicine, Los Angeles, CA; 7Dermatology Research Associates, Los Angeles, CA; 8Enverus Medical, Surrey, BC, Canada; 9University of British Columbia, Vancouver, BC, Canada; 10SKiN Centre for Dermatology, Peterborough, ON, Canada; 11Queen’s University, Kingston, ON, Canada; 12Amgen Inc., Thousand Oaks, CA; 13George Washington University School of Medicine, Washington, DC

Background: Mild to moderate psoriasis may lead to substantial quality-of-life (QOL) impairment, particularly due to involvement of psoriasis in special areas, such as the scalp and nails, or symptoms such as itching. In ADVANCE, apremilast 30 mg BID (APR) demonstrated efficacy in the treatment of mild to moderate psoriasis versus placebo (PBO) at Week 16. We report the Week 32 safety and efficacy results of APR in treating psoriasis symptoms and involvement in special areas, including scalp and nails. 

Methods: ADVANCE was a Phase 3, randomized, double-blind, PBO-controlled study. Adults with mild to moderate plaque psoriasis (static Physician’s Global Assessment [sPGA] score of 2-3 with BSA 2%-15% and PASI score of 2-15) who were biologic naive and inadequately controlled with or intolerant to ≥1 topical therapy were randomized 1:1 to APR or PBO for 16 weeks followed by a 16-week APR extension phase. Efficacy assessments at Weeks 16 and 32 included sPGA and scalp PGA (ScPGA) response (score of 0 [clear] or 1 [almost clear] with ≥2-point reduction from baseline), Nail Psoriasis Severity Index (NAPSI) score change from baseline and achieving score of 0 (NAPSI-0), Whole Body Itch Numeric Rating Scale (WBI-NRS) response (≥4-point reduction from baseline), and a post hoc analysis of achievement of ≥5-point improvement in Dermatology Life Quality Index (DLQI) score or achieving DLQI score of 0 or 1.

Results: Of 595 randomized patients (APR: n=297; PBO: n=298), 503 entered the extension phase. At baseline, 69.1 percent of patients had ScPGA scores ≥2, with slightly more APR-treated patients with ScPGA scores of 3 (moderate) or 4 (severe) than PBO patients. A total of 29.4 percent of patients had NAPSI scores ≥1, and baseline NAPSI scores were similar between APR and PBO groups. At Week 16, statistically significant and clinically meaningful improvements were observed in sPGA response, WBI-NRS, DLQI, and special areas (ScPGA response and NAPSI endpoints) with APR vs PBO (all P<0.05). At Week 32, efficacy was maintained in patients who continued APR treatment for all endpoints (sPGA response [24.9%], ScPGA response [41.1%], NAPSI-0 [38.2%], WBI-NRS [43.4%], DLQI ≥5-point improvement [62.0%], and DLQI 0 or 1 [27.6%]). NAPSI scores decreased with APR treatment at Week 16 and were maintained through Week 32 (−1.6). Similar improvements were observed in patients who switched to APR (sPGA response [29.3%], ScPGA response [49.4%], NAPSI-0 [29.6%], and WBI-NRS [53.1%]). Adverse events were consistent with the known safety profile of APR.

Conclusion: Apremilast treatment resulted in sustained and clinically meaningful improvements in psoriasis symptoms, psoriasis in special areas, and quality of life for patients with mild to moderate psoriasis.

Funding: This study was sponsored by Amgen Inc. Writing support was funded by Amgen and provided by Kristin Carlin, BSPharm, MBA, of Peloton Advantage, LLC, an OPEN Health company, and Dawn Nicewarner, PhD, employee of and stockholder in Amgen Inc.

Disclosures: LSG: AbbVie, Amgen, Arcutis, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member. 

KP: AbbVie, Actelion, Amgen, Astellas Pharma US, Boehringer Ingelheim, Bausch Health, Celgene Corporation, Dermira, Dow Pharmaceuticals, Eli Lilly, Frontier, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co., Inc., Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals, UCB, and Valeant – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant; PSLOAR, PURE – steering committee member.

DP: Amgen, AO Biome, Asana, Brickel Biotech, Celgene Corporation, Dermavant, Dermira, Eli Lilly, Menlo Therapeutics, Merck, Novartis, Ortho, Regeneron, Atacama, Biofrontera, Bristol Myers Squibb, LEO Pharma, Pfizer, Sanofi, and Valeant – honoraria, investigator, advisory board, or data monitoring board member. 

NB: AbbVie, Allergan, Amgen Inc., Biofrontera, Castle, Dermavant, EPI Health, Ferndale, Galderma, ISDIN, LaRoche-Posay, LEO Pharma, Lilly, Ortho, PharmaDerm, Pfizer, Regeneron, Sanofi, Sun Pharma, and Vyne – advisor, consultant, investigator, and/or speaker.

HS: AbbVie, Amgen, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, and UCB – honoraria, grants, and/or research funding as an investigator, advisory board member.

LA: AbbVie, Amgen Inc., Arcutis, Boehringer Ingelheim, Bausch Health/Valeant, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, MedImmune, Merck & Co., Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, and UCB – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, or consultant.

MG: AbbVie, Amgen Inc., Akros, Arcutis, Bausch/Valeant, Boehringer Ingelheim, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co., Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals USA Inc., and UCB – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant.

MC, MP, SC, and HP: Amgen Inc. – employment.

YW: Amgen Inc. – employment at time of study.

LG: AbbVie, Amgen, Arcutis, Dermavant, MC2, Novartis, Lilly, OrthoDerm, Sun Pharma, and UCB – investigator, speaker, and/or consultant.

 

Maintenance of absolute psoriasis area and severity index (PASI) responses with guselkumab through five years (Week 252) among patients who achieved absolute PASI ≤2 at Week 16 in the VOYAGE 1 Study

Presenters: Reich K,1 Gordon KB,2 Andrew Blauvelt A,3 Foley P,4 Leonardi C,5 Landells I,6 Miller M,7 Yang Y,8 Wegner S,9 Shen YK,7 Yin You Y,7 Langley R10

Affiliations: 1Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Germany; 2Medical College of Wisconsin, Milwaukee, WI; 3Oregon Medical Research Center, Portland, OR; 4The University of Melbourne, St. Vincent’s Hospital Melbourne and Probity Medical Research, Skin Health Institute, Carlton, VIC, Australia; 5Central Dermatology, St. Louis, MO; 6Nexus Clinical Research, St. John’s Newfoundland, Canada; 7Janssen Research & Development, LLC, Spring House, PA; 8Janssen Global Services, LLC, Horsham, PA; 9Janssen‐Cilag GmbH, Neuss, Germany; 10Dalhousie University, Halifax, Nova Scotia, Canada

Background: Guselkumab is a fully human monoclonal antibody, selectively blocking interleukin-23 through binding to its p19 subunit. VOYAGE 1 was a Phase 3, randomized, double-blind, placebo- and active comparator-controlled trial of guselkumab in patients with moderate to severe plaque psoriasis. The objective of this post-hoc analysis was to assess long-term maintenance of absolute Psoriasis Area and Severity Index (PASI) responses through 5 years among guselkumab treated patients who achieved absolute PASI ≤2 at Week 16.

Methods: In VOYAGE 1, 837 patients were randomized (2:1:2) to receive guselkumab 100 mg at Weeks 0 and 4, then every eight weeks (q8w; n=329); placebo at Weeks 0, 4, and 12, followed by guselkumab 100mg at Weeks 16 and 20, then q8w (n=174); or adalimumab 80mg at Week 0, 40mg at Week 1, and 40mg q2w through Week 47, followed by guselkumab 100 mg at Week 52 then q8w (n=334). Patients entered open-label guselkumab treatment during Weeks 52 to 252. Absolute PASI thresholds of 0, ≤1, ≤2, ≤3, and ≤5 were evaluated through Week 252 among patients randomized to guselkumab at baseline who achieved absolute PASI ≤2 at Week 16. Efficacy was assessed using nonresponder imputation (NRI) through Week 48 (patients with missing efficacy data, regardless of the reason, were counted as nonresponders after application of treatment failure rules [TFR], which considered nonresponders as those who discontinued study agent due to lack of efficacy or worsening of psoriasis, or use of a protocol-prohibited psoriasis treatment). Starting at Week 52, the analysis was performed using observed data after applying TFR.

Results: The proportions of patients achieving PASI 0 was 66 percent, PASI ≤1 was 80%, PASI ≤2 was 91%, from Week 16 through Week 252 among GUS-treated patients who achieved absolute PASI ≤2 at Week 16 (n=248). Among guselkumab -treated patients who achieved absolute PASI ≤2 at Week 16, 84 percent or greater maintained a PASI ≤2 through Week 252, and 54 percent or greater had a PASI 0 through Week 252. No new safety concerns were reported for guselkumab through Week 264.

Conclusion: In the VOYAGE 1 study, among patients who achieved an absolute PASI ≤2 at Week 16, durable maintenance of absolute PASI responses were observed through Week 252 (5 years) with guselkumab treatment.

Funding: This poster was supported by Janssen Research and Development, LLC.

Disclosures: KR has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, Leo, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, UCB; Professor Reich is co-founder of Moonlake Immunotherapeutics. 

KBG has received research/grant support from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma, and honoraria for consultation from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Janssen, Novartis, and UCB Pharma. A. Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharmaceutical, and UCB Pharma. 

PF has received grant support from AbbVie, Amgen, Celgene, Janssen, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma. He has served as an investigator for AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, BMS, Boehringer Ingelheim, Botanix, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Galderma, Genentech, GSK, Hexima, Janssen, Leo Pharma, Lilly, MedImmune, Melaseq/Geneseq, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB Pharma, and Valeant, He has served on advisory boards for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Galderma, GSK, Janssen, Leo Pharma, Lilly, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Valeant. He has served as a consultant for BMS, Galderma, GenesisCare, Janssen, Leo Pharma, Lilly, Mayne Pharma, MedImmune, Novartis, Pfizer, Roche, UCB Pharma, and Wintermute. He has received travel grants from AbbVie, Galderma, Janssen, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Roche, Sun Pharma, and Sanofi, and has served as a speaker for or received honoraria from AbbVie, Amgen, Celgene, Galderma, GSK, Janssen, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, Sun Pharma, and VCL has served as a consultant/advisory board member and/or investigator and/or speaker for Actavis, Abbvie, Allergan, Amgen, Boehringer-Ingelheim, Celgene, Coherus, Cellceutix, Corrona, Dermira, Eli Lilly, Galderma, Glenmark, Janssen, Leo Pharma, Merck, Novartis, Novella, Pfizer, Sandoz, Sienna, Stiefel, Sun Pharmaceuticals, UCB, Wyeth, and Vitae. I. Landells has served as an advisor, speaker and/or clinical trial investigator for AbbVie, Amgen, Bausch, Celgene, Cipher, Galderma, Janssen, LEO, Lilly, Novartis, Pfizer, Sanofi and Valeant. M. Miller, Y-K. Shen, and Y. You are employees of Janssen Research and Development, LLC, Y-W. Yang is an employee of Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, and S. Wegner is an employee of Janssen-Cilag GmbH, Neuss, Germany; employees may own stock in Johnson & Johnson, of which Janssen is a subsidiary. 

RGL has served and received compensation in the form of grant funding and/or honoraria as principal investigator and is on the scientific advisory board or has served as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sun Pharma, and UCB.

 

Mechanism and proof of concept for a novel, orally delivered, gut-restricted drug candidate for the treatment of psoriasis and other inflammatory diseases

Presenters: Maslin D,1 Ramani K,1 Cartwright ANR,1 Carpenter N,1 Wardwell-Scott L,1 Itano A,1 McHale D1

Affiliations: 1Evelo Biosciences

Background: There is a newly discovered control mechanism for systemic inflammation radiating from the small intestine. Evelo Biosciences is developing pharmaceutical preparations of single strains of gut mucosa-associated microbes that modulate the small intestinal axis (SINTAXTM), enabling systemic inflammation-resolving therapeutic effects with an oral medicine. 

EDP1815 is a pharmaceutical preparation of a single strain of Prevotella histicola. EDP1815 potently attenuates murine models of TH1, TH2, and TH17- inflammation. It is non-replicating and does not colonize the gut, nor alter the microbiome. Using in vivo and ex vivo models, we demonstrate the mechanism by which oral SINTAX medicines affect systemic inflammatory responses through direct action on host cells in the gut. We then evaluate EDP1815 in a Phase 1b clinical study of psoriasis.

Methods: The randomized placebo controlled trial included two cohorts of 12 and 18 patients with mild to moderate psoriasis, randomized 2:1 active:placebo (NCT03733353). EDP1815 was administered once daily for 28 days, with follow-up at Day 42 and was dosed at 1.6×1011 bacterial cells or 8.0×1011 cells per day. Placebo subjects were pooled across both cohorts. The primary endpoint was safety and tolerability. The percentage change in the LSS and the PASI score were measured at baseline, Day 28, and Day 42. 

Results: EDP1815 was well tolerated at both doses, with a safety and tolerability profile comparable to placebo. There were no serious adverse effects. At day 28, the percentage reduction in PASI for both EDP1815 cohorts was 16 percent, compared to 1 percent for placebo. At day 42, the percentage improvement from baseline increased to 21 percent in the high dose cohort.

The percentage reduction in LSS scores at 28 days were 15 percent and 23 percent in the active cohorts, compared to a 1 percent increase in the placebo group. At day 42, the percentage reduction in LSS in the high dose group continued to improve.

Conclusion: The preclinical data begin to explain the mechanism by which engagement of the mucosal immune system in the gut by an orally delivered, gut-restricted SINTAX medicine candidate can modulate systemic inflammation.

The clinical data provide the first clinical evidence of translation of the activity of SINTAX medicines in humans. We see modulation of psoriasis, a systemic inflammatory disease, by a gut-restricted SINTAX medicine. Currently no licensed drugs are known to treat human disease by this mechanism of action.

These data support further clinical development of EDP1815, and open the possibility for a new modality of SINTAX-targeted therapeutics for the treatment of inflammatory diseases.

Funding: Funding provided by Evelo Biosciences.

Disclosures: All authors are employees of Evelo Biosciences. 

 

Mind.Px – Personalized medicine for psoriasis biologic treatment

Presenters: Dickerson TJ,* Lee BI, Montgomery III, P, Boyd S, Andrade E, Abaya C, Boyce C, Tomich T, and Yipeng Wang Y

Background: In the United States, psoriasis affects upward of 3 percent of the population, leading to healthcare costs of >$110 billion annually. In recent years, the emergence of targeted biologic treatments has revolutionized the management of moderate to severe psoriasis patients, with impressive results. However, these clinical gains have come with a concomitant dramatic increase in the spending on higher priced biologic drugs. It generally takes 12 to 16 weeks for clinical response to treatment to be meaningful, and published real world evidence has demonstrated the efficacy of presently available therapies ranging from 27 percent to 64 percent. With the array of biologics available, physicians have been required to implement a trial-and-error paradigm to identify the best drug for a given patient. According to Joint AAD/NPF guidelines, an important need exists to identify biomarkers that can predict the appropriate biologic agent for patients.

Methods: Transcriptomes were collected from subjects (N=232) with a psoriasis diagnosis using a proprietary dermal biomarker patch that allows for simple, rapid, and painless extraction of RNA from the skin. Patient PASI scores also were measured at baseline as well as week 12 and week 16 after drug exposure. Transcriptomes were analyzed using next-generation sequencing (NGS) using standard protocols. The resulting data set (transcriptomic data and clinical outcomes) was used to train and prospectively validate a machine learning-based classifier for each class of biologic.

Results: Using the combined transcriptomic and clinical outcome data set, machine learning classifiers for each biologic class were trained to predict if a patient would achieve a minimum response of PASI75 by Week 12 (IL17i and IL23i) or Week 16 (TNFαi). Interestingly, these classifiers used largely orthogonal biomarkers for predicting response. Overall, the performance of the classifiers were excellent with a combined positive predictive value (PPV) of 91 percent, 79 percent sensitivity, and 86 percent specificity, across all three biologic classes.

Conclusion: By combining the Mindera Health dermal biomarker patch technology with machine learning methods, we have developed a precision medicine test (Mind.Px) that can predict psoriasis patient response to biologic class (TNFαi, IL17i, or IL23i) prior to drug exposure with high positive predictive value. By putting patients on the right biologic the first time, this test can lead to improved patient outcomes, while also potentially translating into tremendous cost savings for healthcare systems. Mind.Px can effectively minimize the trial-and-error approach to the treatment of psoriasis, and provide physicians, patients, and payers with a powerful tool for re-envisioning the management of psoriasis patients.

Funding: Support for this study was provided by Mindera Health.

 

Safety and efficacy of bimekizumab through two years in patients with moderate to severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the BE BRIGHT open-label extension trial

Presenters: Thaçi D,1 Vender R,2 de Rie M,3 Conrad C,4 Pariser D,5 Strober B 6,7 Vanvoorden V,8 Peterson L,9 Madden C,9 de Cuyper D,8 Kimball AB10

Affiliations: 1Institute and Comprehensive Center for Inflammation Medicine, University Hospital of Lübeck, Lübeck, Germany; 2Dermatrials Research Inc., Hamilton, Ontario, Canada; 3Department of Dermatology, Amsterdam University Medical Centres, Amsterdam, Netherlands; 4Department of Dermatology, Lausanne University Hospital, Switzerland; 5Eastern Virginia Medical School and Virginia Clinical Research, Inc, Virginia; 6Yale University, New Haven, Connecticut; 7Central Connecticut Dermatology Research, Cromwell, Connecticut; 8UCB Pharma, Brussels, Belgium; 9UCB Pharma, Raleigh, North Carolina; 10Harvard Medical Faculty Physicians, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Background: In the BE SURE (NCT03412747) Phase 3 trial, bimekizumab (BKZ) demonstrated superior efficacy compared with adalimumab (ADA) in the treatment of moderate to severe plaque psoriasis, with a safety profile comparable to previous BKZ studies.1-3 Given the chronic nature of psoriasis and the loss of response that is observed over time with biologics, it is important to consider longer-term safety and efficacy.4

Methods: In BE SURE, patients were randomized in a 1:1:1 ratio to BKZ 320mg every four weeks (Q4W) for 56 weeks, BKZ 320mg Q4W for 16 weeks then every eight weeks (Q8W) through Weeks 16–56, or ADA 40mg every two weeks for 24 weeks followed by BKZ 320mg Q4W to Week 56. After completing BE SURE, patients could enroll in the BE BRIGHT open-label extension (OLE) (NCT03598790). Dose adjustments (BKZ 320mg Q4W or Q8W) could occur at Week 56 based on whether patients achieved a ≥90% improvement from baseline in the PASI90. The percentage of patients achieving PASI90/100 are reported using modified NRI (mNRI) to account for missing data, based on patients’ initial randomization groups. Treatment-emergent adverse events (TEAEs) were coded using MedDRA v19.0. Exposure‑adjusted incidence rates (EAIRs) are incidences of new cases per 100 patient-years (PY). Safety data are reported through Weeks 24–104. Safety data through Weeks 0–24 have been previously reported.1 

Results: In BE SURE, 478 patients were randomized to BKZ Q4W (N=158), BKZ Q4W/Q8W (N=161), or ADA/BKZ Q4W (N=159). Week 16 PASI90 response rates among BKZ-randomized patients were sustained through to Week 104: 91.2% of BKZ Q4W- and 89.7% of BKZ Q4W/Q8W-randomized patients achieved PASI90 at Week 104 (mNRI). In ADA-randomized patients, PASI90 response rates substantially increased following the switch to BKZ Q4W at Week 24; at Week 104, response rates were similar to those in patients receiving BKZ from baseline. Week 16 PASI 100 response rates were also sustained through to Week 104 for patients randomized to BKZ and improved in patients who switched from adalimumab to BKZ at Week 24.

Through Weeks 24–104, EAIRs of serious TEAEs were 3.3/100 PY with BKZ Q4W, 6.2/100 PY with BKZ Q4W/Q8W and 7.3/100 PY with ADA/BKZ Q4W. One death occurred (BKZ Q4W) which was not considered treatment-related. The three most common TEAEs with BKZ Q4W, Q4W/Q8W and ADA/BKZ Q4W were nasopharyngitis (18.8, 12.3, 17.2/100 PY), oral candidiasis (12.9, 8.8, 18.1/100 PY) and upper respiratory tract infections (7.5, 8.7, 8.0/100 PY).

Conclusion: Clinical responses observed during the first 16 weeks of BE SURE in BKZ-randomized patients were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Switching from ADA to BKZ resulted in a substantial and sustained increase in PASI90 and PASI100 responder rates. BKZ was well tolerated with no new safety signals.

Funding: Funding was provied by UCB Pharma. Medical writing support provided by Costello Medical.

Disclosures: DT: Honoraria for participation on advisory boards, as a speaker and for consultancy from: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS Biopharma, Eli Lilly, Galapagos, Janssen, LEO Pharma, Morphosis, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi Genzyme, and UCB Pharma; research grants received from Celgene, LEO Pharma, and Novartis.

RV: Grants/research support: AbbVie, Amgen, Centocor, Dermira, Dermavant, Eli Lilly, Galderma, GSK, LEO Pharma, Novartis, Merck, Pfizer, Regeneron, Takeda and UCB Pharma; speakers bureau/honoraria: AbbVie, Actelion, Amgen, Bausch-Health, Celgene, Cipher, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer and UCB Pharma; consulting fees: AbbVie, Actelion, Amgen, Bausch-Health, Celgene, Cipher, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Palladin, Pfizer and UCB Pharma.

MDR: Honoraria for participation on advisory boards, as a speaker and for consultancy from: AbbVie, Almirall, Artax Biopharma, Biogen, Celgene, Eli Lilly, Janssen-Cilag, Janssen Pharmaceutica, LEO Pharma, Novartis and UCB Pharma.

CC: Consultant and/or principal investigator in clinical trials for: AbbVie, Actelion, Amgen, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen-Cilag, LEO Pharma, MSD, Novartis, Pfizer, Samsung, Sanofi Genzyme and UCB Pharma.

DP: Honoraria for participation on advisory boards, data safety monitoring boards, consultancy or as an investigator from: Atacama Therapeutics, Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene, Dermira, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, TheraVida, Valeant; grants/research funding: Almirall, Amgen, AOBiome, Asana Biosciences, Bickel Biotechnology, Celgene, Dermavant, Dermira, Eli Lilly, LEO Pharma, Menlo Therapeutics, Merck, Novartis, Novo Nordisk, Ortho Dermatologics, Pfizer and Regeneron. 

BS: Consultant (honoraria) for: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Equillium, GSK, Janssen, LEO Pharma, Meiji Seika Pharma, Mindera, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma; speaker for AbbVie, Amgen, Eli Lilly, Janssen, and Ortho Dermatologics; Scientific Director (consulting fee) for Corrona Psoriasis Registry; investigator for AbbVie, Cara Therapeutics, Corrona Psoriasis Registry, Dermavant, Dermira and Novartis; Editor-in-Chief (honorarium) for Journal of Psoriasis and Psoriatic Arthritis.

VV, LP, CM, DDC: Employees and shareholders of UCB Pharma.

ABK: Consultant and investigator for: AbbVie, Eli Lilly, Janssen, Bristol Myers Squibb, LEO Pharma, Meiji Pharma, Novartis, Pfizer, Regeneron and UCB Pharma; advisor to the Organization of Teratology Information Services (OTIS) and Ventxy Biosciences; fellowship funding from AbbVie and Janssen; Board of Directors: Almirall.

 

Safety and efficacy of once-daily roflumilast cream 0.3%, a potent phosphodiesterase-4 inhibitor, for the treatment of psoriasis in the DERMIS-1 and DERMIS-2 Phase 3 trials

Presenters: Lebwohl M,1 Kircik LH,2 Moore AY,3 Gold LS,4 Del Rosso J,5 Draelos Z,6 Gooderham MJ,7 Green LJ,8 Hebert AA,9 Papp K,10 Bagel J,11 Bhatia N,12 Ferris LK,13 Jones T,14 Kempers SE,15 Pariser D,16 Yamauchi PS,17 Zirwas M,18 Feng A,19 Burnett P,19 Higham RC,19 Berk DR19

Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY; 2Icahn School of Medicine at Mount Sinai, New York, NY, Indiana Medical Center, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, and Skin Sciences, PLLC, Louisville, KY; 3Arlington Research Center, Arlington, TX, Baylor University Medical Center, Dallas, TX; 4Henry Ford Medical Center, Detroit, MI; 5JDR Dermatology Research Center, LLC, Las Vegas, NV; 6Dermatology Consulting Services, High Point, NC; 7SkiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 8George Washington University School of Medicine, Rockville, MD; 9UT Health McGovern Medical School, Houston, TX; 10Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 11Psoriasis Treatment Center of Central New Jersey, Windsor, NJ; 12Therapeutics Clinical Research, San Diego, CA; 13University of Pittsburgh, Department of Dermatology, Pittsburgh, PA; 14U.S. Dermatology Partners Bryan, Bryan, TX;15Minnesota Clinical Study Center, Fridley, MN; 16Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA; 17David Geffen School of Medicine at UCLA, Los Angeles, and Dermatology Institute & Skin Care Center, Inc., Santa Monica, CA; 18Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH; 19Arcutis Biotherapeutics, Inc., Westlake Village, CA

Background: Roflumilast cream 0.3%, a selective and highly potent phosphodiesterase-4 inhibitor, is being investigated as a nonsteroidal, once-daily treatment for long-term management of psoriasis. We describe the effects of once-daily roflumilast cream 0.3% on plaque psoriasis during two Phase 3, randomized, double-blind, vehicle-controlled, multi-center trials. 

Methods: DERMIS-1 (N=439; NCT04211363) and DERMIS-2 (N=442; NCT04211389) were identical Phase 3 trials conducted in patients (≥2 years) with psoriasis involving 2-20% of body surface area (BSA). Patients were randomized 2:1 to once-daily roflumilast cream 0.3% or vehicle for eight weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (IGA status of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. 

Results: In both studies, significantly more roflumilast-treated patients than vehicle-treated patients achieved IGA Success (DERMIS-1: 42.4% vs. 6.1%; DERMIS-2: 37.5% vs 6.9%, P<0.001 for both) at Week 8. Statistically significant differences favoring roflumilast were observed for multiple secondary endpoints, including percentage of patients achieving intertriginous-IGA Success (DERMIS-1: 71.2% vs. 13.8%; DERMIS-2: 68.1% vs. 18.5%, P<0.01), percentage of patients achieving 75% reduction in Psoriasis Area Severity Index (DERMIS-1: 41.6% vs. 7.6%; DERMIS-2: 39.0% vs 5.3%, P<0.0001), percentage of patients achieving 90% reduction in Psoriasis Area Severity Index (DERMIS-1: 22.4% vs. 2.3%; DERMIS-2: 17.0% vs 2.3%, P<0.0001), and percentage of patients with baseline Worst Itch-Numeric Rating Scale ≥4 achieving a 4-point reduction in WI-NRS (DERMIS-1: 67.5% vs 26.8%; DERMIS-2: 69.4% vs 35.6%, P<0.0001) at Week 8. Roflumilast also demonstrated superior improvement from baseline in BSA compared with vehicle at Weeks 2-8 (P≤0.01). The improvements in investigator-assessed disease severity were consistent with improvements in patient-reported disease severity and burden as indicated by a significantly greater reduction in total Psoriasis Symptom Diary score compared with vehicle-treated patients. At Week 8, least square mean difference in percentage change from baseline total PSD score compared with vehicle treatment was -54.3% in DERMIS-1 and -38.8% in DERMIS-2 (P<0.001). Local tolerability was highly favorable as reported by patient and investigator assessment of irritation, burning, and stinging. On investigator-rated local tolerability, over 96 percent of patients in each group had no evidence of irritation at Week 4 or Week 8. On patient-rated local tolerability, scores were low (favorable) and similar to vehicle at all timepoints. Overall incidence of treatment-emergent adverse events (TEAE), serious adverse events, and TEAEs leading to discontinuation were low with similar rates between roflumilast and vehicle across both studies. 

Conclusion: Results from these two Phase 3 studies indicate that roflumilast cream 0.3% demonstrated superior improvement across multiple efficacy endpoints versus vehicle cream with onset as early as 2 weeks and was well-tolerated with low rates of application site and treatment-related AEs in patients with psoriasis.

Funding: Sponsored by Arcutis Biotherapeutics, Inc.

 

Secukinumab dosing every two weeks versus every four weeks demonstrates superior efficacy in adult patients with plaque psoriasis weighing 90 kg or more, and benefits PASI 90 non-responder patients who up-titrate at Week 16

Presenters: Reich K,1 Augustin M,2 Yamauchi P,3 Pinter A,4 Bagel J,5 Dahale S,6 Djimopoulos J,7 Paguet B,8 Patekar M,8 Deborah Keefe7

Affiliations: 1Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3Dermatology Institute & Skin Care Center, Santa Monica, CA; 4University of Frankfurt, Department of Dermatology, Venereology and Allergology, Frankfurt am Main, Germany; 5Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; 6IQVIA, Mumbai, India; 7Novartis Pharmaceuticals Corporation, East Hanover, NJ; 8Novartis Pharma AG, Basel, Switzerland

Background: Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A. This study (NCT03504852) investigated the efficacy and safety of 300 mg secukinumab every two weeks (Q2W) vs. every four weeks (Q4W) to treat psoriasis in patients weighing ≥90 kg. 

Methods: Patients with moderate to severe plaque psoriasis received 300mg secukinumab Q2W or Q4W (1:1) for 48 weeks. Psoriasis Area and Severity Index (PASI) 90 response (primary endpoint) and Investigator’s Global Assessment mod 2011 (IGA) 0/1 response (secondary endpoint) were assessed at Week 16. At Week 16, Q4W PASI 90 non-responders were reallocated to remain on Q4W or switch to Q2W until Week 48, and the efficacy of this up-titration was assessed. 

Results: At Week 16, 73.2% of Q2W-treated (n=165) and 55.5% of Q4W-treated (n=166) patients achieved a PASI 90 response (one-sided P-value=0.0003). At Week 52, Q2W dosing (n=165) demonstrated higher PASI 90 (76.4% vs. 52.4%) and IGA 0/1 responses (75.9% vs. 55.6%) vs. Q4W (n=83). PASI 90 non-responders who up-titrated to the Q2W regimen (n=31) showed higher PASI 90 responses at Week 32 (16 weeks post-up-titration; 38.7% vs. 16.5%) vs. those who remained on Q4W (n=40). Safety results were comparable across different treatment arms and consistent with the established secukinumab safety profile.

Conclusion: 300mg secukinumab Q2W demonstrated superior and sustained efficacy compared to Q4W in moderate to severe plaque psoriasis patients weighing ≥90 kg. In the PASI 90 non-responder population, patients derived additional benefits from up-titration at Week 16 to a Q2W regimen.

Funding: This investigation was sponsored by Novartis Pharma AG, Basel, Switzerland. The authors thank Daniella Taylor (Novartis Pharmaceuticals UK Ltd, London, UK) for editorial and medical writing support, which was funded by Novartis Pharma AG, Basel, Switzerland in accordance with the Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Disclosures: KR has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Amgen, Biogen-Idec, Celgene, Centocor, Covagen, Eli Lilly, Forward Pharma, GSK, Janssen-Cilag, Leo Pharma, Medac, MSD, Novartis, Pfizer, Vertex, Takeda, and Xenoport. 

MA has served as consultant for, or has been a paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Abbvie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli-Lilly, GSK, Janssen-Cilag, Leo, Medac, Merck, MSD, Novartis, Pfizer, UCB, and Xenoport. P. Yamauchi has served as an investigator for Amgen, Celgene, Dermira, Galderma, Janssen, LEO Pharma, Eli Lilly, MedImmune, Novartis, Pfizer, Regeneron, and Sandoz, and has served as an advisor and/or speaker for AbbVie, Amgen, Baxter, Celgene, Dermira, Galderma, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Regeneron. 

AP has worked as an investigator and/or speaker and/or advisor for AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Boehringer-Ingelheim, Celgene, GSK, Eli-Lilly, Galderma, Hexal, Janssen, LEO-Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough, and UCB Pharma. 

JB has received research funds payable to Psoriasis Treatment Center from AbbVie, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Corrona LLC, Dermavant Sciences, LTD, Dermira, UCB, Eli Lilly and Company, Glenmark Pharmaceuticals Ltd, Janssen Biotech, Kadmon Corporation, Leo Pharma, Lycera Corp, Menlo Therapueutics, Novartis, Pfizer, Regeneron Pharmaceuticals, Sun Pharma, Taro Pharmaceutical Industries Ltd, and Ortho Dermatologics; he has received consultant fees from AbbVie, Amgen, Celgene Corporation, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Biotech, Novartis, Sun Pharmaceutical Industries Ltd, UCB; and he has received fees for speaking from AbbVie, Celgene Corporation, Eli Lilly, Janssen Biotech, and Novartis.
SD is employed by IQVIA. 

JD, BP, MP, and DK are employed by Novartis.

 

Tapinarof cream 1% once daily for plaque psoriasis: long-term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent

Presenters: Strober B,1 Gold LS,2 Robert Bissonnette R,3 Armstrong A,4 Blauvelt A,5 Leon Kircik L,6,7 Brown PM8, Tallman AM,8 Lebwohl M

Affiliations: 1Yale University, New Haven & Central Connecticut Dermatology Research, Cromwell, CT, 2Henry Ford Health System, Detroit, MI, 3Innovaderm Research Inc., Montreal, QC, Canada, 4Keck School of Medicine at University of Southern California, Los Angeles, CA, 5Oregon Medical Research Center, Portland, OR, 6Skin Sciences PLLC, Louisville, KY, 7Icahn School of Medicine at Mount Sinai, New York, NY, 8Dermavant Sciences, Inc., Morrisville, NC

Background: In two double-blind, 12-week pivotal trials (PSOARING 1 & 2), tapinarof cream 1% once daily (QD) demonstrated significant efficacy versus vehicle and was well tolerated in adults with mild-to-severe plaque psoriasis. Tapinarof also maintained efficacy after a 12-week phase-2b trial, warranting investigation of a potential remittive effect. PSOARING 3 was a long-term extension trial designed to assess the safety and efficacy of tapinarof (including duration of remittive effect off-therapy and durability of response on-therapy) during repeated, intermittent treatment, based on individual patient Physician Global Assessment (PGA) score.

Methods: Eligible PSOARING 1 & 2 completers could enroll in PSOARING 3 for 40-weeks’ open-label treatment followed by 4-weeks’ follow-up. Patients entering with PGA≥1 received tapinarof 1% QD until disease clearance (PGA=0/clear). Patients entering with/achieving PGA=0 discontinued treatment and were monitored for remittive effect (off-therapy maintenance of PGA=0/1). Patients with disease worsening (PGA≥2) were re-treated until PGA=0. Efficacy endpoints included median time from PGA=0 to first PGA≥2 and proportion of patients with PGA=0/1 after treatment. 

Results: 91.6 percent of eligible patients (n=763) enrolled in PSOARING 3. Common treatment-emergent adverse events, which were mostly mild/moderate and at application sites, were folliculitis (22.7%), contact dermatitis (5.5%) and upper respiratory tract infection (4.7%). Incidence/severity of folliculitis and contact dermatitis remained stable and were associated with low discontinuation rates (1.2% and 1.4%, respectively). Efficacy continued to improve beyond the 12-week pivotal trials. Overall, 40.9 percent (n=312) of patients achieved complete disease clearance (PGA=0) at least once and 58.2 percent (n=302) entering with PGA≥2 achieved PGA=0/1. Consistent efficacy was observed across weeks overall, despite intermittent treatment and regardless of prior treatment with tapinarof or vehicle in the pivotal trials: overall, 10.4 percent (n=79) had PGA=0 and 31.6 percent (n=240) had PGA=0/1 at entry; at week 40, 16.9 percent (n=126) had PGA=0 and 44.3 percent (n=330) had PGA=0/1. Median duration of remittive effect off-drug was 4 months (115 days) for patients entering with PGA=0 (n=79). Among patients entering with/achieving, PGA=0 (n=312), mean duration of remittive effect off-drug was >4 months (130 days). Durability of response with no tachyphylaxis for up to 52 weeks was demonstrated.

Conclusion: Tapinarof cream 1% QD, a non-steroidal psoriasis therapy, was well tolerated long-term, consistent with previously reported pivotal trials. A high rate of complete disease clearance, ~4-month remittive effect off-therapy, no tachyphylaxis, and consistent efficacy irrespective of intermittent treatment are key attributes of tapinarof, confirmed by these data.

Funding: Funding was provided by Dermavant Sciences, Inc.


ROSACEA


A novel formulation of BPO for long-term management of rosacea

Presenters: Bhatia ND,1 Lain E,2 Baldwin H,3,4 Brantman S,5 Del Rosso JQ,6 Sivamani RK7,8 

Affiliations: 1Therapeutics Clinical Research; 2Sanova Dermatology; 3The Acne Treatment & Research Center; 4Rutgers Robert Wood Johnson Medical Center; 5Galderma Laboratories, LP; 6JDR Research; 7Integrative Skin Science and Research; 8Pacific Skin Institute

Background: Benzoyl peroxide (BPO) has demonstrated efficacy in rosacea treatment; however, despite the promising data, the use of traditional formulations has been limited by subject intolerability. In rosacea skin, tolerability reactions observed with previous formulations of BPO included burning, itching, and stinging. A new formulation of encapsulated BPO has been developed that is both efficacious and tolerable for subjects with moderate to severe rosacea. In the formulation reported here, BPO is enclosed in a silica microcapsule that gradually releases BPO to the skin.

Two previous 12-week Phase 3 trials of encapsulated benzoyl peroxide cream, 5% (E-BPO) demonstrated significant efficacy, rapid onset of action as early as Week 2, and good safety and tolerability at Week 12. This report summarizes the results from the up-to-52-week extension of the two Phase 3 trials with the primary objective of evaluating the long-term safety of E-BPO in subjects with moderate to severe rosacea.

Methods: 547 adult subjects (≥18 years old who had an Investigator Global Assessment [IGA] of Grade 3 or 4, ≥15 inflammatory lesions, and ≤2 nodules) with moderate or severe rosacea were enrolled in the 40-week extension of the two 12-week, double-blind, vehicle-controlled Phase 3 trials. 363 subjects enrolled in the extension were previously treated with E-BPO and 184 were previously treated with vehicle during Phase 3. All subjects were assigned to treatment with E-BPO. Subjects were followed for up to 40 weeks in the extension (for a total of up to 52 weeks). Subjects were on treatment only when IGA >1. The primary objective of this long-term safety study was to determine the nature, frequency, and severity of adverse events (AEs) associated with E-BPO for up to 52 weeks. This study also measured the proportion of subjects achieving an IGA success rating of “clear” or “almost clear” at the end of study (Week 40). Additional assessments included erythema and telangiectasia scores measured from baseline to week 40, a relapse assessment, and a Rosacea Quality of Life (RosaQoL) questionnaire assessment.

Results: No clinically significant safety findings were reported in this study. E-BPO was generally safe and well tolerated by study participants. AEs related to study drug and reported by more than 1 percent of subjects included application site erythema (1.1%) and application site pain (1.1%). At the end of the 52-week evaluation, 73.2 percent of subjects achieved success. The median number of treatment-free days until relapse was 58 days. Results from the RosaQoL questionnaire found that subjects had improvement in total score, symptom subscale score, function subscale score, and emotional subscale score from baseline to the end of the trial.

Conclusion: In this long-term extension of two Phase 3 randomized, controlled trials, E-BPO applied for up to 52 weeks in subjects with rosacea demonstrated progressive and lasting clinical improvement. Efficacy was demonstrated by the percentage of subjects achieving IGA success and reduction in erythema. Importantly, E-BPO demonstrated excellent cutaneous safety and tolerability in rosacea skin.

Funding: Study funded by Sol-Gel Technologies Ltd.; poster support provided by Galderma Laboratories, L.P., Fort Worth, TX.

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