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A novel nitric oxide-releasing gel led to significantly more patients achieving complete clearance of their lesions from molluscum contagiosum infections compared with a vehicle control, and was safe and well tolerated, a phase III trial demonstrated.

In the study of nearly 900 patients, 32.4% of those treated with berdazimer gel had complete lesion clearance at week 12, as compared with 19.7% of those treated with vehicle (OR 2.0, 95% CI 1.5-2.8, P<0.001), reported Tomoko Maeda-Chubachi, MD, PhD, of developer Novan in Durham, North Carolina, and colleagues.

And more patients at this time point randomized to the active arm in the so-called B-SIMPLE4 trial discontinued treatment for lesion clearance (14.4% vs 8.9%), according to the findings in .

Most commonly diagnosed in children, molluscum contagiosum is a highly contagious skin infection caused by the molluscipoxvirus, explained Maeda-Chubachi and colleagues. In the U.S., roughly 6 million people each year are affected by the condition, which causes lesions lasting for months to years that can cause discomfort and lead to scarring.

No FDA-approved therapy currently exists, the group noted, and treatment options may include off-label medications with limited evidence to support them, or procedures such as cryotherapy or lesion destruction with topical cantharidin that requires multiple trips to the clinic.

According to the study, nitric oxide functions as an immune modulator with broad-spectrum antimicrobial properties, and berdazimer gel allows for the safe and stable delivery of it to sites of infection or inflammation.

In the current trial, the treatment-emergent adverse event (AE) rate with berdazimer was 43% (vs 23% with vehicle), and AEs tended to be mild in severity, with the most common being pain at the application site (14.4% vs 4.7%, respectively), erythema (5.6% vs 1.1%), and pruritis (5.6% vs 0.9%). Skin reactions to the treatment were common in the early weeks but improved over time, the researchers noted.

AEs leading to treatment discontinuation occurred in 4.1% of berdazimer patients and 0.7% of controls, and severe AEs occurred in five and two patients, respectively.

"For years, many children and their parents seeking evaluation and treatment for MC [molluscum contagiosum] have been counseled to wait it out," wrote Vikash Oza, MD, of New York University Grossman School of Medicine in New York City, in an . "Although MC in an otherwise healthy child is self-resolving, the average case lasts 13.5 months, and 13% of cases are not resolved within 2 years. Understandably, many families look to fast-forward their child's experience with the infection."

Oza noted that the findings with berdazimer gel mirror those of VP-102 (cantharidin delivered via a single-use applicator), which showed a complete clearance rate of 50% in children with molluscum contagiosum lesions at 84 days, as compared with 15% in patients receiving vehicle, in a pooled analysis of two randomized trials.

"To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort. We are still far from that ideal," said Oza.

But both berdazimer gel and VP-102 have the potential to be the first FDA-approved therapies for molluscum contagiosum -- "a step in the right direction," he added.

Developer Novan is for berdazimer gel by the end of 2022. While VP-102 is further along in the NDA process, Verrica, the company developing that product, has from the agency.

B-SIMPLE4 randomized 891 patients to either berdazimer gel 10.3% solution or vehicle. Patients were an average of about 6.5 years old, over 85% were white, and the study was roughly split between males and females. At 12 weeks, a similar proportion of patients had a lesion count performed: 88.5% and 88.8% for the berdazimer and vehicle groups, respectively. The primary endpoint was a lesion count of 0 at this time point.

On average, baseline lesion counts were 23.1 in the study arm and 20.5 in the control arm, and about half of the patients had no inflammation. Patients were living with their lesions for an average of roughly 12 months (range 0-193).

For secondary outcomes, complete clearance among patients with a lesion count at week 8 was achieved in 19.6% of those on berdazimer compared with 11.6% of those receiving vehicle (P=0.001). And 43.5% of patients on berdazimer had one or zero lesions at week 12, compared with 24.6% of those receiving vehicle (P<0.001). The study met its other secondary endpoints as well.

The findings from B-SIMPLE4 -- which was recommended by the FDA to confirm benefit -- build upon two prior phase III trials (B-SIMPLE1 and B-SIMPLE2) showing complete clearance rates of 28% and 21% with berdazimer in patients with molluscum contagiosum-related lesions.

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