VYNE Therapeutics announced disappointing topline results from its phase 2b trial evaluating repibresib gel in nonsegmental vitiligo, with the study failing to meet its primary endpoint and key secondary objectives. The randomized, double-blind, vehicle-controlled trial evaluated 177 subjects across 45 North American sites but did not demonstrate the expected therapeutic benefit over placebo.
The trial missed its primary endpoint of achieving at least 50% improvement in Facial Vitiligo Area Scoring Index (F-VASI50) at week 24, with only 19.5% of patients in the highest dose group (3%) reaching this threshold compared to 23.4% in the vehicle group. Similarly, the key secondary endpoint of F-VASI75 showed minimal differences across treatment arms, with the 3% dose achieving 9.8% response versus 6.4% for vehicle.
Unexpected Vehicle Response Complicates Results
"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 Therapeutics. The company attributed the trial's failure to an unusually high vehicle effect that masked potential treatment benefits.
Dropout rates varied significantly between treatment arms, with the repibresib 3% group experiencing a 36.6% discontinuation rate compared to only 10.6% in the vehicle group. The repibresib 2% and 1% groups had discontinuation rates of 30.2% and 26.1%, respectively.
Promising Signals in Secondary Measures
Despite missing primary endpoints, the trial showed nominally statistically significant treatment effects for the highest dose in key secondary measures. The repibresib 3% group demonstrated a mean 43.6% reduction from baseline in F-VASI scores compared to 25.6% for vehicle (p=0.0020). Similarly, total vitiligo area scores (T-VASI) showed a 28.3% improvement versus 16.2% for vehicle (p=0.0436).
Safety Profile Raises Concerns
The trial revealed a higher rate of treatment-emergent adverse events for repibresib-treated subjects compared to vehicle. Application site pain emerged as the most frequent adverse event, occurring in 14.0% of the 3% dose group, 13.7% of the 1% group, 5.9% of the 2% group, and 3.8% of vehicle-treated patients.
Eight participants receiving repibresib discontinued due to adverse events, while no vehicle-treated subjects discontinued for safety reasons. Most skin-related adverse events were mild in severity (76.0%) and resolved during the study, with no clear dose-dependent pattern observed. One serious adverse event—cholelithiasis without obstruction—occurred in the 1% group but was deemed unrelated to treatment.
Strategic Pivot and Partnership Pursuit
Based on these results, VYNE will discontinue treatment in the ongoing extension phase and terminate the trial. The company plans to seek a development and commercialization partner for repibresib while conducting a thorough evaluation of the complete dataset.
"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 stated. The company expects to provide updates on its strategic plans, including development of oral BET inhibitor VYN202, in the coming weeks.
Financial Position and Platform Potential
VYNE reported approximately $39.6 million in cash, cash equivalents, and investments as of June 30, 2025. The company's BET inhibitor platform includes repibresib, designed as a "soft" drug for local administration with low systemic exposure, and VYN202, an oral small molecule with enhanced selectivity for BD2 versus BD1 bromodomains.
The setback represents a significant challenge for VYNE's vitiligo program, though the company maintains that vitiligo remains an area of significant unmet medical need. The trial's completion marks a critical juncture for the company's development strategy as it seeks external partnerships to advance its BET inhibitor technologies.
