Vyne Therapeutics' BET Inhibitor Fails Phase 2 Vitiligo Trial, Stock Plummets

Vyne Therapeutics faced a significant setback as its lead candidate, repibresib gel, failed to meet primary and secondary endpoints in a phase 2b vitiligo trial. The news sent shockwaves through the company, resulting in a dramatic 74% drop in stock price during premarket trading on Wednesday.

Trial Results and Safety Concerns

The study, which evaluated various doses of repibresib gel, a pan-bromodomain BET inhibitor, in 177 patients with non-segmental vitiligo, failed to achieve its primary endpoint of a more than 50% improvement in facial vitiligo score. Additionally, the secondary endpoint of a 75% improvement was not met.

Safety data revealed a higher rate of treatment-emergent adverse events in the repibresib gel group compared to the vehicle cohort. The most common adverse event was application site pain, affecting 14% of patients receiving the highest 3% dose of repibresib, compared to 3.8% in the vehicle group. Eight patients discontinued treatment due to adverse events in the repibresib group, while none did so in the vehicle group.

Company Response and Future Plans

Despite the disappointing results, Vyne Therapeutics' CEO David Domzalski remains optimistic about the company's InhiBET BET inhibitor platform. The company is conducting a thorough evaluation of the full dataset and considering its strategic next steps.

Vyne has terminated the current study and is seeking a partner for repibresib. The company plans to provide an update on its plans for both repibresib and another BET inhibitor, VYN202, in the coming weeks. VYN202's phase 1b study was recently abandoned due to FDA concerns about testicular toxicity.

Broader Implications for BET Inhibitors

The failure of repibresib gel raises questions about the efficacy and safety of BET inhibitors in dermatological applications. While research into BET inhibitors for cancer treatment has shown promise, it has also revealed potential hematologic and gastrointestinal adverse effects.

Vyne's approach with repibresib, using a topical gel delivery format, was intended to avoid safety concerns associated with systemic use of pan-BD BET inhibitors. However, the higher rate of adverse events in the treatment group suggests that challenges remain in developing safe and effective BET inhibitors for dermatological conditions.