Phase 2b Repibresib Study Falls Short of Key Goals

Image Credit: © DermNet

Today, Vyne Therapeutics announced topline results from its phase 2b trial evaluating repibresib gel in nonsegmental vitiligo. Vyne, a clinical stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need, said the trial 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 (F-VASI50) at week 24 compared to vehicle.¹

The trial, which completed enrollment in January of this year, evaluated 177 subjects.² The company said it also missed a key secondary endpoint of F-VASI75, however it showed a "nominally statistically significant treatment effect" for the highest dose cohort in another key secondary endpoint: Percent change-from-baseline (CFB) in F-VASI score at week 24 compared to vehicle (Repibresib 3%: -43.6% v. Vehicle: -25.6%), and an exploratory endpoint of percent CFB in T-VASI score at week 24 compared to vehicle (Repibresib 3%: -28.3% v. Vehicle: -16.2%).

“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, president and chief executive officer of VYNE, in a news release. “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.”

In the release, the company stated it 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 (Repibresib 3%: 36.6%; Repibresib 2%: 30.2%; Repibresib 1%: 26.1% and vehicle: 10.6%). Based on these data, Vyne stated it will discontinue the treatment in the ongoing extension phase of the trial, therefore terminating the trial.

Conducted in 45 sites in North America, 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 (QD) at 1%, 2%, and 3% concentrations, versus vehicle in patients with nonsegmental vitiligo. According to the release from the company, there was a higher rate of treatment emergent adverse events (TEAE) for subjects receiving repibresib gel compared to vehicle. The most common TEAEs (>5%) were reportedly cutaneous in nature.

Vyne stated the most common adverse event in the trial was application site pain, occurring more frequently in repibresib-treated groups than in the vehicle group. Eight participants using repibresib discontinued due to adverse events, compared to none in the vehicle group. The release stated most skin-related TEAEs were mild and resolved during the study, with no clear dose-dependent trend. One serious adverse event—cholelithiasis without obstruction—occurred in the repibresib 1% group but was not drug-related. No increased risk of thrombocytopenia or serious gastrointestinal events was observed.
References

1. VYNE Therapeutics announces topline results from phase 2b trial with repibresib gel in nonsegmental vitiligo. News Release. VYNE Therapeutics. Published July 30, 2025. Accessed July 30, 2025. https://finance.yahoo.com/news/vyne-therapeutics-announces-topline-results-120000626.html?guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&guce_referrer_sig=AQAAAMjhWKx95Pnt4-rfiW363sBvpQn9665GK39KmdHSHgAlA8h5K_2KIVP9xw414-3W5XA8EPua-OTvt_h6Z7XHVXFnzZIZzlQwAaNwyYOuiDfC3adT5nX8q6a9mGUlaryQrbDTSmNH8mNeEgVNut19mxwW0Pt2kD4w7HmaGUa68zT4&guccounter=2
2. VYNE therapeutics completes enrollment in phase 2b trial evaluating VYN201 for the treatment of nonsegmental vitiligo. News Release. VYNE Therapeutics. Published January 6, 2025. Accessed July 30, 2025. https://vynetherapeutics.com/uncategorized/vyne-therapeutics-completes-enrollment-in-phase-2b-trial-evaluating-vyn201-for-the-treatment-of-nonsegmental-vitiligo/