Improving Molluscum Treatment Options: Overcoming the Challenge of Poor Adherence

J Clin Aesthet Dermatol. 2025;18(7):12–16.

by Yasir Al-Dojaily, MD, and Steven R. Feldman, MD, PhD

Dr. Al-Dojaily is with the Department of General Surgery at Wake Forest University School of Medicine in Winston-Salem, North Carolina. Dr. Feldman is with the Department of Dermatology at the Center for Dermatology Research at Wake Forest University School of Medicine in Winston-Salem, North Carolina; the Department of Pathology at Wake Forest University School of Medicine in Winston-Salem, North Carolina; and the Department of Social Sciences and Health Policy at Wake Forest University School of Medicine in Winston-Salem, North Carolina.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors declare no conflicts of interest relevant to the content of this article.

Abstract: Objective: This review aims to understand medication adherence and its influence on efficacy for existing and novel topical treatments for molluscum contagiosum. Methods: A PubMed search was performed on clinical studies from 2000 to 2023 assessing adherence and treatment efficacy for topical and non-topical therapies used to treat molluscum. Results: Adherence to individual topical treatments for molluscum is poor and limits their utility in clinical practice, despite demonstrated safety, painless administration, and advantages for pediatric and home use. Studies suggested lower adherence for topical rather than procedural treatments due to delayed effects, long treatment duration, and uncertain perceived benefits. New topical agents, VP-102 (ie, cantharidin 0.7% drug-device combination) and SB206 (ie, berdazimer gel 10.3%), showed promising efficacy in clinical trials, but their ability to address adherence is unclear. Limitations: There is a lack of sufficient clinical studies on topical medications for molluscum contagiosum, limiting our overall understanding of adherence and practical efficacy. Conclusion: Several studies suggest that commonly used topical medications for molluscum suffer from poor adherence, reducing treatment efficacy. Addressing adherence to these medications may promote the utility of topicals to deliver the need for safe, painless, and efficacious treatments for molluscum. Larger, well-designed trials accounting for adherence are needed before evidence-based treatment recommendations can be made for topical molluscum treatments. Our findings propose that in-office topicals like cantharidin may overcome nonadherence and enhance efficacy compared to daily home-administered topical medications. Keywords: Molluscum contagiosum, treatment adherence, topical medications, cantharidin, pediatric dermatology, berdazimer gel

Introduction

Molluscum contagiosum (MC) is a skin infection caused by the DNA poxvirus molluscum contagiosum virus (MCV). MC is most prevalent in children (5.1–11.5% globally).^1,2 Lesions often occur on the trunk, face, and genitalia, characterized by firm, dome-shaped, umbilicated, white or flesh-colored papules under 1cm in diameter. Transmission occurs through direct skin-to-skin contact, autoinoculation, or indirectly through fomites.³ Lesions may be accompanied by pruritus, pain, and bacterial superinfection.⁴ Immunocompromised individuals may have widespread, large lesions.

MC is a frequent dermatologic complaint presenting with concerns for further transmission, discomfort, social stigma, or cosmetic appearance. The disease burden on patients and caregivers is considerable.⁵ Patients may try unapproved treatments that might make matters worse; such treatments should be avoided.⁶ Treatments include physical removal of lesions and various topical, intralesional, and systemic medications (Table 1). There is currently insufficient evidence to determine the best management strategy for MC.⁷ Treatment strategies are presently made case-by-case based on clinician experience and patient and disease factors.¹

Despite the high prevalence of MC, efficacy data on topical treatments are limited by small sample sizes, inconsistent study parameters, and variations in treatment formulation and regimen. A 2017 Cochrane review of 22 studies concluded that no reliable evidence-based recommendations could be made for the treatment of MC, except that topical 5% imiquimod is likely not more effective than placebo and likely more harmful due to serious application site reactions.⁷

There is a need for painless, safe, convenient, and efficacious topical treatments for MC and for better information on the efficacy and safety of these treatments. Promising new topicals have been tested and await United States Food and Drug Administration (FDA) approval. However, adherence to topical medications is often poor and may limit efficacy.⁸ How will new MC topicals address the limitations of poor adherence? The current review aims to explore the influence of treatment adherence on the efficacy of existing and experimental topical medications for MC. Understanding adherence will help identify opportunities to improve topical treatments for MC.

MC Topicals and the Adherence Hurdle

Medication nonadherence is a major public health issue associated with higher healthcare costs and worse treatment outcomes.⁹ Topical medications are vulnerable to nonadherence due to frequently low patient satisfaction.¹⁰ Topicals are an important tool for managing MC and present a major advantage over unpleasant procedural approaches. However, the efficacy of topical treatments is likely limited by poor adherence.¹⁰ While adherence to oral drugs is also considered poor, the rate of adherence is significantly lower for topicals.⁸ Patients with psoriasis prefer systemic therapy over topical therapy, with adherence rates as low as 50 percent for topical treatments.¹¹ Perhaps systemic treatments for MC, namely oral cimetidine, would enjoy better adherence than topicals; unfortunately, there is no evidence that oral cimetidine is effective for MC.²

Patient satisfaction determines adherence to topical medications and stems from several factors including convenience of use, mechanical and sensory medication properties, adverse events, timing of effect, and time needed for application.^8,10 Although patients and their caregivers may be motivated to treat their MC, dissatisfaction with their topicals will likely lead to nonadherence. Current topical treatments for MC are slow and require diligence. Many treatment regimens call for up to twice-daily application of the drug to each lesion over a period of months.² Considering the majority of children with MC have between 10 and 50 lesions,¹² frequent topical application may be too time-consuming to adhere to. The delay in lesion clearance might further discourage patients from using their topicals long enough to achieve a therapeutic benefit. In one study, adherence to a curettage procedure was greater than two MC topicals used daily for 90 days.¹³ Lower satisfaction was attributed to slower acting treatment. Adverse events can also reduce adherence, although topical MC treatments are generally well-tolerated with the exception of imiquimod.^2,14

A major limitation to our understanding of adherence in MC management is a lack of sufficient data. Most of the studies in the 2017 Cochrane review did not provide information on treatment adherence.⁷ Differences in adherence may partly explain why the reported efficacy of individual MC therapies vary so greatly.¹⁵ Understanding treatment adherence is critical for accurately measuring treatment efficacy. The studies that have reported adherence are primarily clinical trials; adherence to topical treatments for MC influences treatment efficacy. In a randomized placebo-controlled trial on topical potassium hydroxide, patients with high treatment adherence had better clearance with drug (70%) compared to placebo (16%), whereas the low adherence groups showed no difference between drug and placebo.¹⁶ The data on adherence is further skewed by the fact that participation in clinical trials enhances treatment adherence compared to clinical practice.¹⁷ This is partly due the higher frequency of follow-up visits during clinical trials and “white coat compliance,” the phenomenon that patients adhere better to medications around the time of office visits.¹⁸

To summarize, in the absence of information specific to MC, data on other topicals suggest that current MC topicals likely have poor adherence due to long and time-consuming regimens, unclear efficacy, and delayed resolution. More information is clearly needed on adherence to better understand the efficacy of topical treatments for MC and improve their utility.

Will New Topicals Overcome Treatment Adherence?

Two novel topical agents for MC have recently been approved for MC and have shown promising results in Phase II and III trials. The first treatment, investigated in trials under the name VP-102 (YCANTH®; Verrica Pharmaceuticals Inc., West Chester, Pennsylvania), is a novel drug-device preparation containing cantharidin, while the second, called SB206 (ZELSUVMI™; Novan Inc., Durham, North Carolina), is a nitric oxide-releasing topical gel containing berdazimer sodium. VP-102 and SB206 hope to meet the need for safe and efficacious topical treatments for MC. Treatment adherence will be an important factor in determining their potential for success.

VP-102. Cantharidin has long been used as a topical treatment for MC. It activates serine proteases in epidermal keratinocytes to induce acantholysis and intraepidermal blistering.² Concentrations of 0.7 to 0.9% with or without occlusion are administered in-office by physicians every 2 to 4 weeks until clearance of lesions is achieved.¹⁹ The initial application is painless, making cantharidin well-tolerated in children. After 1 to 2 days, a blister forms that can be painful and prone to infection, followed by scarless healing. Due to concerns for deeper blistering, cantharidin is usually avoided for lesions on thin skin, including the face and groin. Until recently, efficacy and safety data were limited to small studies evaluating varying preparations of the drug.²⁰ Prior to the approval of cantharidin 0.7% drug-device combination, there were no FDA-approved cantharidin products, and the drug was not widely available, with no uniform formulation. The use of occlusion and the application tools, which include cotton swabs, wooden sticks, and toothpicks, are not standardized.¹⁹ There was uncertainty over what the best regimen, dosage, formulation, and application of cantharidin is.

VP-102 is a proprietary standardized drug-device combination containing cantharidin 0.7% (w/v) for the treatment of MC.²¹ In an open-label Phase II trial assessing the safety and efficacy of VP-102, 33 participants were treated with VP-102 to each MC lesion once every 21 days until complete resolution for a maximum of four treatment cycles.²² Complete clearance was 48.5 percent by Day 84 with a mean reduction in lesion count of 90.4 percent. Quality of life index scores has a “mild effect on quality of life” at the start of treatment and “no effect” by Day 84. There were no serious adverse events and no excessive blistering. The most common reaction was pain. Systemic absorption was found to be negligible.

Cantharidin Application in Molluscum Patients-1 (CAMP-1) and CAMP-2 were two identical Phase III, randomized, double-blind, vehicle-controlled trials comparing the safety and efficacy of VP-102 for MC treatment versus vehicle control.²³ In total, 528 participants were randomized to receive VP-102 or vehicle to all MC lesions once every 21 days until complete lesion clearance for a maximum of four cycles. Complete clearance by Day 84 was 46.3 percent and 54.0 percent for VP-102 compared to 17.9 percent and 13.4 percent for vehicle, for CAMP-1 and CAMP-2, respectively. The mean reduction in lesion count by Day 84 in CAMP-1 was 69 percent for VP-102 versus a 20-percent increase for those receiving vehicle. Mean reduction of lesions at Day 84 in CAMP-2 was 83 percent for VP-102 and 19 percent for vehicle. VP-102 had greater complete clearance rates after a single treatment in CAMP-1 (VP-102: 11.3% versus vehicle: 3.7%) and for all subsequent treatment intervals. Almost all participants receiving VP-102 experienced at least one mild to moderate adverse event compared to 58.8 percent receiving vehicle. The most common reactions were blistering, pain, and pruritus. Infection-related adverse events were similar between VP-102 and vehicle. The study discontinuation rates were 6.4 percent for VP-102 and 4.6 percent for vehicle. Approximately 1.9 percent of participants receiving VP-102 discontinued treatment because of adverse events, mostly application site blistering, compared to 0.5 percent for vehicle.

In a post-hoc analysis on the safety and efficacy of VP-102 for different anatomic regions, VP-102 consistently outperformed vehicle at each anatomic site studied.²⁰ These sites included the face, neck, and groin. The incidence of adverse events was relatively consistent across each anatomic region and was comparable to those reported in CAMP-1 and CAMP-2, with the exception of higher rates of pain reported for the head/neck region and lower rates of pain for the groin.

VP-102 may overcome several of the challenges of adherence expected to affect other MC topical treatments. Firstly, the treatment regimen is simple, consisting of a single application of the topical once every three weeks. Although treatment duration may be up to 84 days based on the trials, this would only represent four doses of the topical. It may be easier to adhere to the infrequent dosing of VP-102 compared to other topicals which involve daily application over a similar time period.¹⁵ Treatment effect occurred quickly after only the first application.²³ Furthermore, the rapid appearance of blisters after application may convince some patients that the topical is working, encouraging further treatment satisfaction and motivation for future treatment cycles. As an in-office, physician-administered intervention, adherence to VP-102 can be assured, unlike home-administered treatments.¹⁸ Conversely, patients may consider in-office treatments to be burdensome as they require effort and time to attend. Compared to in-office surgery, VP-102 is painless, easier to administer, and has minimal risk of scarring.

SB206. Nitric oxide (NO) is a colorless gas that serves as a key messenger molecule in vertebrae. NO acts as both an immune modulator and a direct antimicrobial agent via reactive oxidative and nitrogenous species, which can disrupt viral replication.²¹ Berdazimer, the NO-releasing molecule in SB206, is thought to exert antiviral effects on MCV through protein nitrosylation and NF-κB modulation.²⁴

A multicenter, randomized, double-blind, vehicle-controlled Phase II trial evaluating efficacy and tolerability of three concentrations of berdazimer sodium (4%, 8%, and 12%) and two dosing regimens (once daily 12% versus twice daily 4%, 8%, and 12% for 12 weeks) of topical SB206 concluded that SB206 12% once daily had the optimal balance of lesion clearance and tolerability.²⁵ A total of 256 participants were randomized to each arm, 216 of which completed the 12-week treatment course. Participants were at least two years old (mean age 7 years) and had a range of 3 to 70 MC lesions at baseline. Complete clearance at the end of treatment (lesion count of 0), was 20.0 percent for the vehicle group compared to 13.2 percent, 41.0 percent, 35.1 percent, and 41.9 percent of participants receiving SB206 4% twice daily, 8% twice daily, 12% twice daily, and 12% once daily, respectively. Adverse events were reported by 43.6 percent of participants receiving SB206 versus 28.8 percent for vehicle. Most adverse events were mild to moderate application site reactions, including itching, dryness, burning, and erythema (most common). SB206 12% once daily was associated with fewer application-site reactions compared to 8% twice daily.

Following this was a Phase III, multicenter, vehicle-controlled, double-blind trial measuring the safety and efficacy of topical berdazimer gel 10.3% (the free-base equivalent of berdazimer sodium 12%).²⁴ Participants were at least six months old with 3 to 70 MC lesions. 891 participants were randomized to receive berdazimer or vehicle once daily for 12 weeks. The rate of treatment completion was roughly 90 percent for both groups. At 12 weeks, complete clearance (lesion counts of 0 or 1) was higher for those receiving berdazimer (32.4%) than vehicle (19.7%). Complete clearance at Weeks 4 and 8 was also higher for berdazimer. The mean reduction in lesion count was 57.5 percent for berdazimer versus 31.3 percent for vehicle at Week 12, and was greater for the berdazimer group as early as Week 2. Berdazimer was well-tolerated, causing mostly mild or moderate application-site reactions resembling those from the Phase II trial. Severe reactions were reported by 1.1 percent of participants receiving berdazimer, which included pain, erythema, and dermatitis. Local skin reaction scores were highest in Weeks 2 and 4 of treatment and lowest at Week 12. Further, 4.1 percent of those receiving berdazimer had adverse events associated with treatment discontinuation compared to 0.7 percent for vehicle.

The large Phase II and III trials appear to show good efficacy and safety data for berdazimer gel for the treatment for MC. Berdazimer is now FDA-approved for once daily application per lesion for up to 12 weeks. Individual treatment adherence was not reported in either trial. Treatment discontinuation due to treatment-related adverse events was small and suggested good drug tolerability. However, the remaining majority of study dropouts were not fully explained. The attrition rates in trials can be a warning sign for poor adherence in clinical practice for reasons including lack of efficacy, delayed effect, and unfavorable user experience. Interestingly, the trials showed the greatest changes over time for both lesion clearance and adverse events over the first two and four weeks of treatment. A gradual decrease in adherence over the course of the study may explain the observed attenuation of treatment effect. In studies of psoriasis and atopic dermatitis, topical adherence drops rapidly from the first day of use.^26,27 Adherence for berdazimer will likely be worse in clinical practice compared to the clinical trial setting, potentially limiting its practical efficacy.^17,18 While topical berdazimer is a promising home-use, once daily topical for MC, data on adherence will be important for determining its treatment potential.

Conclusion

MC is a common dermatologic condition that currently lacks a consensus on the best management approach. There is a need for good topical treatments as alternatives to cryosurgery or curettage, which can be painful and traumatic for children. Two novel topical drugs, VP-102 and SB206, have been approved for MC, and having performed well in large randomized-controlled human trials, without major safety concerns.

Poor adherence to treatment is a likely barrier to the utility and efficacy of topicals for MC. Long treatment courses, delayed clinical effect, and uncertain efficacy of the current topical medications may be contributing to patient dissatisfaction and nonadherence. The success of these treatments in clinical trials often exceeds what we see in real practice due to better treatment adherence during clinical studies. Simple, effective, and painless in-office topical treatments are promising and may overcome the challenges of adherence to home-use topical medications.

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