VYNE says Phase 2B trial with repibresib gel did not meet primary endpoint

VYNE Therapeutics (VYNE) announced topline results from its Phase 2b trial evaluating Repibresib gel in nonsegmental vitiligo. The trial, which evaluated 177 subjects, did not meet its primary endpoint of the proportion of subjects achieving an improvement in Facial Vitiligo Area Scoring Index of at least 50% from baseline at week 24 compared to vehicle. The trial also missed a key secondary endpoint of F-VASI75. However, the trial showed a nominally statistically significant treatment effect for the highest dose cohort in a key secondary endpoint, percent change-from-baseline in F-VASI score at week 24 compared to vehicle, and an exploratory endpoint of percent CFB in T-VASI score at week 24 compared to vehicle. In evaluating the results of the trial, the Company believes the results were impacted by an unusually high vehicle effect and further impacted by a higher-than-expected dropout rate in the active arms of the trial relative to vehicle. Based on these data, the company will discontinue treatment in the ongoing extension phase of the trial and will terminate the trial.The Phase 2b trial was a randomized double-blind, vehicle-controlled, multi-center trial that evaluated the safety and efficacy of Repibresib dosed once daily at 1%, 2% and 3% concentrations, versus vehicle in 177 subjects with nonsegmental vitiligo. The trial was conducted at 45 sites in North America and assessed various efficacy endpoints, including the primary endpoint of the proportion of subjects achieving F-VASI50 at Week 24 versus vehicle, as well as key secondary endpoints, which included the proportion of subjects achieving F-VASI75 at Week 24, percent CFB in F-VASI score at week 24 and exploratory endpoints including percent CFB in T-VASI score at week 24. “We are disappointed with the results of our Phase 2b trial, which were impacted by an unexpectedly high treatment effect in the vehicle arm and a high discontinuation rate in the active arms,” said David Domzalski, CEO. “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. Vitiligo remains an area of significant unmet need and we are grateful to the patients, investigators, and clinical staff who participated in the trial. 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. We intend to seek a development and commercialization partner for Repibresib and we will provide an update on our plans, including those for our oral BET inhibitor VYN202, in the coming weeks.” While the Company has not finalized its full financial results for the quarter ended June 30, 2025, the Company expects to report that it had cash, cash equivalents and investments of approximately $39.6M as of June 30, 2025. There was a higher rate of treatment emergent adverse events for subjects receiving Repibresib gel compared to vehicle. The most common TEAEs were cutaneous in nature. The most frequent adverse event was application site pain. There were 8 subjects receiving Repibresib gel that discontinued due to an AE compared to none in the vehicle. The majority of skin-related TEAEs were mild in severity and resolved during study conduct and there was no clear dose-dependent increase in frequency of skin-related TEAEs. There was one treatment emergent serious adverse event, cholelithiasis without obstruction, not drug related in the Repibresib 1% cohort, and there was no increased risk of thrombocytopenia or GI-related serious adverse events.