The company emphasizes that the data was “near statistically significant” in B-SIMPLE2 and was statistically significant in the secondary endpoint and several pre-specified sensitivity analyses.
Morrisville, North Carolina-based Novan reported topline results from its Phase III B-SIMPLE trial for SB206 for molluscum contagiosum. Although the trial did not hit its primary endpoint in B-SIMPLE1 and B-SIMPLE2, the company says that multiple sensitivity analyses support continuation. As a result, the topline results are for efficacy data only. Company shares plunged 74% in premarket trading on the news.
Molluscum contagiosum is a common viral infection of the skin. It results in round, firm, painless bumps that can range in size from a pinhead to a pencil eraser, according to the Mayo Clinic. If scratched or injured, the infection can spread to surrounding skin. It also spreads through person-to-person contact and via contact with infected objects. It is most common in children, although it can affect adults, particularly adults with compromised immune system. In adults with a normal immune system, molluscum involving the genitals is a sexually transmitted infection. The bumps typically disappear within a year without treatment, but sometimes “doctor-assisted removal” is performed.
Novan indicates it plans to use B-SIMPLE2 as one of the confirmatory trials for a New Drug Application (NDA) submission. It also plans to support and confirm B-SIMPLE 2 with a confirmatory Phase III trial that it expects to launch in April 2020, subject to additional funding and discussions with the U.S. Food and Drug Administration. Otherwise, Novan says its NDA submission timeline remains consistent, with a possible submission in the second quarter of 2021.
The B-SIMPLE program is made up of two multi-center, randomized, double-blind, vehicle-controlled pivotal trials of SB206, a topical nitric oxide-releasing therapy. The program evaluated 707 patients aged six months and older randomized 2:1, drug to vehicle (placebo).
The primary endpoint was the proportion of patients with complete clearance of all treatable molluscum lesions at the 12-week point. The company emphasizes that the data was “near statistically significant” in B-SIMPLE2 and was statistically significant in the secondary endpoint and several pre-specified sensitivity analyses. The secondary endpoint was complete clearance at Week 8. They also say that B-SIMPLE1, which also did not show statistical significance in the primary endpoint, was supportive and consistent with the B-SIMPLE2 results.
Novan indicated in its latest quarterly filing on September 30, 2019, that it had $22.5 million in total cash, cash equivalents and restricted cash. This was targeted to fund operations into the first quarter of 2020, not including the effect of any potential stock sales under its agreement with Aspire Capital Fund.
Novan noted that the p-value of the B-SIMPLE2 trial was 0.062. The p-value is the probability of obtaining the observed result. Generally, a p value of less than 0.05 is considered statistically significant and less than 0.001 as statistically highly significant. By tweaking the primary endpoint population by using a per protocol approach or by modifying how it handled missing data, the company brought the p-value down below the threshold for statistical significance.
By taking that approach and adding in the secondary endpoint data, the company thinks there’s enough positive data to warrant filing an NDA. However, the B-SIMPLE1 trial doesn’t really support that, so they plan to run a Phase III, assuming they can convince investors to help fund it, which doesn’t seem too promising after the stock plunged 74%. It will also depend on whether the FDA agrees to the scheme.
