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NEW ORLEANS -- Almost 40% of patients with molluscum contagiosum, some with dozens of lesions, had complete or near-complete clearance after 12 weeks of nitric oxide-releasing gel, the largest-ever randomized trial of the skin disease showed.

Overall, 30% of patients randomized to topical berdazimer had complete clearance of lesions and 39.3% had zero or one lesion. The outcomes represented a 10-15% absolute improvement versus vehicle. A subgroup analysis showed consistent results across key patient groups, including ages 6-12 years, lesion count, and disease duration.

Adolescents and teenagers as well as Black/African-American patients did not achieve as "statistically robust complete clearance rates," probably because of small sample size, reported John Browning, MD, of Texas Dermatology in San Antonio, at the American Academy of Dermatology annual meeting.

"This integrated efficacy analysis reveals that berdazimer 10.3% gel results in greater complete clearance rates than vehicle after 12 weeks with once-daily topical applications," said Browning. "Favorable efficacy trends were seen as early as week 2, and efficacy results were consistent across most subgroups."

"If approved by the FDA, this will be the first prescription medication indicated for molluscum contagiosum that could be applied by a patient or caregiver, rather than in an office by a healthcare provider," he added.

An approval decision is expected by early 2024, he said.

During a discussion that followed the presentation, an unidentified questioner asked Browning about treatment-related pain and skin irritation, noting that patients in the trial were as young as 6 months. Browning said the gel compound is non-irritating.

"Massively statistically significant and without a lot of side effects," he noted.

Caused by a poxvirus, molluscum contagiosum affects about 6 million Americans, most of them children. The infection manifests as small, round, firm, umbilicated bumps that are often painless. The condition is associated with multiple psychosocial complications, including stigma, disfiguring lesions and scars, and bullying, said Browning. As many as three-fourths of affected children receive no treatment.

Berdazimer is a new chemical entity consisting of a polysiloxane backbone bound to N-diazeniumdiolate NO donors. The gel is co-administered with a proton donor that promotes NO release. The drug's mechanism of action remains unclear, but NO has antimicrobial and antiviral activity, said Browning. Molluscum contagiosum produces proteins that evade host immunity.

In laboratory studies, berdazimer reduced viral replication and reduced expression of molluscum contagiosum protein associated with evasion of host immunity.

"It is hypothesized that these effects may decrease virus quantity, increase immune surveillance, activate NF-kappa B, and increase apoptosis," said Browning.

Berdazimer gel was evaluated in three parallel randomized, multicenter, vehicle-controlled trials involving 1,600 children and adults with molluscum contagiosum. Patients were randomized to the active gel or vehicle, applied once daily for 12 weeks by the patient or caregiver.

The primary endpoint of the three trials was the proportion of patients with complete clearance of all treatable lesions at week 12. The data were combined into an integrated analysis.

The study population had a mean age just under 7 years, with even sex distribution. The time from symptom onset was about 1 year. About 60% of patients had fewer than 20 lesions, and the rest had more. Fewer than 10% had a history of atopic dermatitis.

The primary analysis showed that patients randomized to berdazimer gel were almost twice as likely to achieve complete clearance at 12 weeks (OR 1.753, 95% CI 1.376-2.223, P<0.0001). A "clear positive treatment effect" (P<0.0001) was evident for patients 6-12 years, with a baseline lesion count <20, disease duration >6 months, and no history of atopic dermatitis. The treatment effect was even clearer for a 12-week outcome of 0-1 lesions (OR 2.062, 95% CI 1.642-2.591, P<0.0001).

Browning acknowledged limitations of the study: all sites were in the U.S., there was no assessment of lesion size, and there was a lack of statistical significance in certain subgroups.

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