ZELSUVMI Topical gel Ref.[107468] Active ingredients: Berdazimer

The pharmacodynamics of ZELSUVMI are unknown.

Plasma hydrolyzed MAP3 (hMAP3), a structural marker for berdazimer, and nitrate levels were evaluated in n=34 subjects 2 to 12 years of age with MC. Subjects applied ZELSUVMI oncedaily for two weeks to a total treatment area of 484 cm² (mean lesion count=34), applying a mean dose of approximately 3 mL/day. No subjects had quantifiable plasma hMAP3 concentrations on day 1; two subjects had quantifiable concentrations on day 15. Mean plasma nitrate levels were similar on days 1 and 15 and remained relatively flat during the PK sampling period (baseline through 1, 3, and 6 hours post-application).

There were no apparent differences in methemoglobin levels throughout the study.

The carcinogenic potential of berdazimer gel was assessed in a 2-year dermal mouse carcinogenicity study. There were no drug-related tumor findings associated with daily topical administration of berdazimer gel to mice at doses up to 4% berdazimer gel.

Berdazimer was mutagenic in a bacterial mutagenicity assay (Ames assay) but was not clastogenic in an in vitro chromosomal aberration assay in human peripheral blood lymphocytes or in an in vivo micronucleus assay in rats.

There were no berdazimer related effects on male or female fertility and early embryonic parameters in rats at oral doses up to 189 mg/kg/day.

The efficacy of ZELSUVMI was evaluated in 3 multicenter, randomized, double-blind, parallelgroup, vehicle-controlled trials in subjects with MC (Trials 1, 2, and 3; NCT04535531, NCT03927703, and NCT03927716, respectively). Trial 1 enrolled 891 subjects, Trial 2 enrolled 355 subjects, and Trial 3 enrolled 352 subjects. Subjects were randomized 1:1 in Trial 1, and 2:1 in Trials 2 and 3 to receive ZELSUVMI or vehicle applied to MC lesions once daily for up to 12 weeks.

In the three trials, 3% of subjects were less than 2 years of age and 96% of subjects were 2 to 17 years of age. The trial population included 51% male, 88% White, 6% Black, and 6% Other; for ethnicity, 21% of subjects identified as Hispanic/Latino, 78% as non-Hispanic/Latino, and 1% were not reported. Subjects had 3-70 baseline MC lesions. At baseline, the average MC lesion count was 20.2.

The primary efficacy endpoint was the proportion of subjects achieving complete clearance at Week 12. Complete clearance was defined as the subject having a total MC lesion count of 0 at assessment. The key secondary efficacy endpoint was complete clearance rate at Week 8.

Efficacy was demonstrated in Trials 1 and 2. The results are summarized in Table 2.

Table 2. Complete Clearance Rate at Week 12 and Week 8 in Subjects with MC in Trials 1 and 2:

In Trial 3, the complete clearance rates at Week 12 were 26% versus 22% for ZELSUVMI and vehicle, respectively, with 95% confidence interval (-5%, 14%).