Treating Molluscum Contagiosum: Current Choices vs the Future Pipeline

Molluscum contagiosum (MC) treatment can be a point of contention for parents of children with the viral skin condition and their physicians. Parents are often insistent on treatment, fearing secondary infection, transmission to other family members, scarring from lesions, or simply the embarrassment that can result from having as many as hundreds of round, fleshy bumps on the skin. Doctors, on the other hand, may be hesitant to treat, trusting the virus will eventually run its course. Some are uncomfortable treating the condition due to a lack of experience or a dissatisfaction with existing treatments, including cryotherapy, curettage, and blistering agents such as cantharidin, which may eliminate the lesions but does not treat lesions that may not yet be apparent. 

“Regarding those pesky molluscum bodies, there are many off-label therapies that are currently being used,” said Stephen W. Stripling, MD, a practicing pediatrician in the Charleston, SC, area and one of seven practitioners interviewed recently concerning MC treatment and prescribing habits. “With so many options, no single one has risen to the top as being a best therapy or drug of choice. Therapy needs to be individualized, and in a self-resolving condition like molluscum contagiosum, sometimes the best ‘medicine’ is to simply observe and wait it out.”

Treatment Differences Among Specialties 
Treatment choices – including whether to treat – vary widely among practitioners and specialties, with dermatologists being more likely than pediatricians to administer treatment, according to the interviews. 

Annette Murphy, a dermatology physician assistant at Associates in Dermatology in Orlando, FL, for example, said she has treated nearly all of her patients with MC she has seen, while Dr Stripling believes the best treatment is no treatment at all. Most practitioners, however, fall somewhere in between, the interviews revealed.

Amy Paller, MD, professor and chair of dermatology at Northwestern University Feinberg School of Medicine and a pediatric dermatologist at the Lurie Children’s Hospital of Chicago (IL), said she ends up treating about 80% of her patients with MC and often sees children whose parents are frustrated by the ineffective topical treatments or lack of treatment offered by pediatricians. Diana Stafford, MD, a board-certified pediatrician in private practice in San Diego, CA, said she treats about 40%.

When pediatricians treat MC, they are more likely to choose conservative treatment, using topical preparations such as salicylic acid, tretinoin, or imiquimod. In contrast, dermatologists tend to take a more aggressive approach, the experts acknowledged. 

“The pediatricians probably never do cryotherapy or curettage,” said Rebecca Baxt, MD, a board-certified dermatologist and owner of BAXT CosMedical in Paramus, NJ, and clinical assistant professor at New York University School of Medicine. “In my experience and opinion, [pediatricians] usually either tell the patients or the parents to leave it alone, [that] it’s going to go away on its own, or they give them the salicylic acid or maybe the imiquimod, although imiquimod doesn’t work all that well.” 

Dermatologists, on the other hand, are more likely to use cantharidin or curettage, said David S. Reitman, MD, associate professor of pediatrics and attending adolescent medicine physician at MedStar Georgetown University Hospital in Washington, DC. 

“If I am going to use a low pH blistering agent, also known as a vesicant,” adds Dr Stripling, “I make sure that the family is well-informed and document in the chart about risks. I have had more than one family return after treatment from me or a local dermatologist with frustration and anger about painful blisters, albeit temporary to their child.” 

Other Factors in Choosing Treatment
In some cases, treatment choice depends on factors such as the number and location of the lesions and the age and skin color of the patient. For example, Murphy said she would consider curettage for a few lesions and if those lesions are “on the back and the parents really want to do it.” For the face, however, she would choose a treatment less likely to cause scarring such as tretinoin or imiquimod. Because cryotherapy can leave a nonpigmented scar, Murphy will not use it on someone who is darkly pigmented.

A major reason many choose cantharidin is because it is painless in the office, in contrast to other destructive techniques, and only a minority of children experience painful blistering when the cantharidin is used correctly. Cantharidin also does not scar, in contrast to the risks of cryotherapy and aggressive curettage, but it may take several serial treatments to clear molluscum entirely.

Some practitioners use a combination of treatments. “Sometimes I have them using the cream at home, and then when they come into my office, we’ll do cryotherapy,” said Dr Baxt.  “So, we’ll often do combo therapy so they’re doing something while they’re at home.” 

The providers, as a whole, did not recommend over-the-counter (OTC) preparations to their patients with the exception of salicylic acid. “Because none of them have undergone any sort of scientific testing, I don’t recommend them,” said Brandi M. Kenner-Bell, MD, attending physician in dermatology and faculty member at Northwestern University Feinberg School of Medicine. “If patients or parents come in and they feel like the OTC product they’re using is working, then I don’t advise them to stop. But I don’t recommend any OTC ones.” 

The providers, as a whole, also did not recommend homeopathic, herbal, or natural products. Even those who treated MC regularly admitted good treatment options were lacking. 

Desired Treatment Characteristics 
When asked about characteristics of treatments they would like to have for MC, the ability to target the virus topped the list. “It would be nice to have something that were specifically antiviral, just as we have for herpes infections,” said Dr Paller.  

The next characteristics would be less painful for patients and more convenient for caregivers. “I think if we had something that we could do in the office that was not painful and not going to scar and would take care of it in one or two visits, that would be great,” said Murphy. “We wouldn’t have to rely on parents to put it on.”

Physical treatments such as curettage or cryotherapy can be painful, and the blistering from cantharidin, if it occurrs, “can be really painful. Topicals, especially tretinoin, can subject the family to a topical medicine for weeks that might give them dermatitis, or it may not work at all,” said Dr Kenner-Bell. “We do not have a consistently reliable, pain-free, hassle-free alternative for something that’s super common. What we need is a 99% effective pain free option.”

“They don’t want to do something every day. They want the quick fix at the office,” said Dr Baxt. “Probably 90% of patients would want treatment if it’s a one-time treatment,” said Dr Reitman. “They’d like to come in, have it done, be out of there, and not think about it again. So, they want an in-office procedure, in and out, and no more. And if there’s a little bit of irritation, they would tolerate that over having to come back two more times because they don’t want to have to deal with compliance issues and all that stuff.”

Treatments in the Pipeline
Two experimental treatments – a novel standardized preparation of topical cantharidin, VP-102, and a topical nitric oxide product candidate, SB206 – are showing promise in clinical trials. VP-102, a formulation of 0.7% cantharidin solution, is supplied in a single-use applicator to provide consistent delivery and long-term drug stability.¹ SB206 uses Novan Inc.’s ability to deploy nitric oxide in solid form in localized formulations.² Rather than being administered in a doctor’s office, it is applied by the patient or caregiver.

In two placebo-controlled trials presented at the 2019 American Academy of Dermatology Annual Meeting in March,¹ VP-102 effectively cleared lesions in patients with MC. In the two trials, a combined 528 patients aged 2 to 60 years (mean age, approximately 7 years) were randomized to treatment or vehicle. About 30% of participants had prior treatment. The baseline lesion count ranged from 1 to 184.

At day 84, the proportion of patients in the VP-102 arm who achieved complete clearance of lesions was 46% in the first trial and 54% in second, compared with 18% and 13%, respectively, among controls (P<.0001). By day 84, the lesion count had decreased by a mean of 69% and 83% in the treatment groups, compared with 20% and 19%, respectively, among controls. 

Most adverse events were mild, although five patients discontinued the studies because of treatment-emergent adverse events. Vesiculation was a common adverse event in the VP-102 group; pruritus and application-site pain were reported as well.

Phase 2 SB206 trials of patients over 2 years of age with at least 3, and as many as 70, lesions also showed efficacy in clearing molluscum lesions. Statistically significant efficacy signal was observed with SB206 12% once-daily (QD) as early as 2 weeks in the percent change from baseline as well as in the proportion of patients with at least a 75% reduction in lesion count. There were few discontinuations due to adverse effects across the SB206 treatment, and none were reported with SB206 12% QD treatment group.

The 12% QD treatment is currently being assessed in a phase 3 program. Top line results of the phase 3 trial are targeted to be no later than early in the first quarter of 2020. If approved, SB206 would be the first FDA-approved treatment for MC. 

Dr Stripling is in the process of completing his third clinical trial on MC.  “I am excited about future options for treating molluscum if the therapeutic and safety data return of value in the FDA’s opinion. Driving the immune response against molluscum seems a more palatable option given the current ‘therapies’ are often painful to the children and sometimes cause scarring.”

References
1. Eichenfield L. CAMP-1 (cantharidin application in molluscum patients) and CAMP-2: phase 3, randomized, double-blind, placebo-controlled, pivotal studies investigating VP-102, a drug-device combination contatining a novel topical formulation of cantharidin, for the treatment of molluscum contagiosum. Presented at: 2019 AAD Annual Meeting; March 2, 2019; Washington, DC.

2. Herbert AA, Siegfried EC, Durham T, et al. Efficacy and tolerability of an investigational nitric oxide-releasing topical gel in patients with molluscum contagiosum: a randomized clinical trial [published online October 3, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.09.064