The bad news keeps on creeping toward Vyne Therapeutics’ BET inhibitor platform. Weeks after the biotech gave up on a psoriasis trial of one drug that was lumbered with a partial clinical hold, the company’s lead candidate has now failed a midstage vitiligo trial.
Vyne had been evaluating various doses of repibresib gel, a pan-bromodomain BET inhibitor, in a phase 2b study of 177 patients with non-segmental vitiligo. The study failed to reach either its primary endpoint of the proportion of subjects achieving a more than 50% improvement in their facial vitiligo score or the secondary endpoint of patients who saw a 75% improvement.
The news sent Vyne’s already battered stock crashing 74% to just 37 cents in premarket trading Wednesday from a Tuesday closing price of $1.44.
The safety data didn’t make for much happier reading, either. There was a higher rate of treatment-emergent adverse events in the repibresib gel cohort compared to those who received vehicle, Vyne explained in the July 30 release.
The most common adverse event was pain where the gel was applied, which affected 14% of patients who received the highest—3%—dose of repibresib compared to 3.8% of the vehicle cohort. A total of eight patients who received repibresib gel discontinued their treatment due to an adverse event compared to none in the vehicle group, Vyne noted.
One serious adverse event, asymptomatic gallstones, was observed in the repibresib 1% cohort, but this was not considered to be related to the treatment.
Searching for a silver lining, Vyne pointed to a nominally statistically significant treatment effect among the highest dose cohort in a different facial vitiligo score. The company also blamed “an unusually high vehicle effect” as well as a “higher-than-expected dropout rate in the active arms” as potential contributors to the trial’s fail.
For now, the company is terminating the study while it seeks a partner for repibresib.
“Although we missed our F-VASI50 and F-VASI75 endpoints, we did see a meaningful reduction in the percent change from baseline in both F-VASI and T-VASI for our highest dose and are conducting a thorough evaluation of the full dataset to analyze any other data that may inform the results and our strategic next steps,” Vyne CEO David Domzalski said in the July 30 release.
“Despite this outcome, we remain confident in the potential of our InhiBET BET inhibitor platform as a promising and innovative mechanistic approach for the treatment of a broad range of serious immune-mediated diseases,” Domzalski added.
Vyne abandoned a phase 1b study of another BET inhibitor, dubbed VYN202, earlier this month after the FDA required a fresh preclinical study to fully allay concerns about testicular toxicity. The biotech said at the time that it would begin to lay out a road map for VYN202 once it had seen the top-line results from today’s repibresib vitiligo study.
Domzalski said in this morning’s release that the company will provide an update on its plans for both repibresib and VYN202 “in the coming weeks.”
Research into the use of BET inhibitors to treat cancer has shown the mechanism can cause hematologic and gastrointestinal adverse effects. Seeking to avoid those outcomes, Vyne designed VYN202 to be selective for the BD2 portion of the protein. The choice reflected evidence that BD2 regulates gene expression of pro-inflammatory mediators while BD1 modulates cell cycling and homeostatic functions.
Although repibresib also inhibits BD1, the topical gel delivery format is meant to sidestep safety concerns associated with the systemic use of pan-BD BET inhibitors.