Novan Therapeutics topical nitric oxide drug candidate SB204 for the treatment of acne vulgaris, demonstrated statistically significant reductions in the percent change of non-inflammatory (white heads and black heads) and inflammatory (larger red bumps and pustules) lesions in Phase 2b studies. The 12-Week study, reported by the company, demonstrated positive findings with all doses of SB204 compared to Vehicle.  SB204 demonstrated excellent cutaneous tolerability with no treatment-related serious adverse events in over 400 dosed subjects to date.  

Based on these results and having completed an End-of-Phase 2 meeting with the FDA, Novan plans to initiate two pivotal Phase 3 trials with SB204 once daily in the first quarter of 2016, targeting enrollment of 1,300 subjects per trial.

“The magnitude of separation from Vehicle we are observing with a once daily monotherapy is comparable to the separation on acne lesions observed for commercially available combination products utilizing two active agents. We engineered a new chemical entity that uses nitric oxide to target multiple aspects of acne pathology, including the elimination of P. acnes without the use of an antibiotic, reduction of sebum excretion, and decrease of inflammation,” said Novan’s president Nathan Stasko, PhD in a statement.

In Novan’s double-blind, vehicle-controlled Phase 2 study conducted across 20 sites in the United States, 213 subjects were randomized to five treatment arms: SB204 2% twice daily, SB204 4% once daily, SB204 4% twice daily and Vehicle once or twice daily and treated for up to 12 weeks.  Data from Vehicle treated subjects were pooled for analysis.  All doses of SB204 showed statistically significant reductions in the percent change of non-inflammatory and inflammatory lesions compared to Vehicle at the 12-week endpoint (intent-to-treat population).  At the end of treatment, the only dose group to be statistically significant in both absolute change and percent change for both lesion types was the SB204 4% once daily treatment arm.  The absolute change from baseline in inflammatory lesions was -11.3 (42%) for 4% once daily and -5.8 (19%) for Vehicle (p=0.004) and the absolute change from baseline in non-inflammatory lesions was -14.1 (37%) for 4% once daily and -7.6 (17%) for Vehicle (p=0.032).  

In a time-to-event analysis, the 4% once daily treatment demonstrated a time-to-median improvement of  4.1 weeks compared to 11.6 weeks for Vehicle (p=0.014 as defined by a 35% reduction in inflammatory lesions).    A 6% difference between the pooled SB204-treated subjects and Vehicle-treated subjects was observed in the Investigator Global Assessment (IGA) endpoint.  While not statistically significant, this difference in IGA enables the power calculations for future Phase 3 pivotal studies with a 95% confidence interval.    At the end of 12 weeks of treatment, <5% of the subjects had a cutaneous tolerability score of ‘moderate’ for any of the local tolerability assessments (erythema, dryness, scaling, itching, burning/stinging) with zero reported subjects having any severe local application site reactions.