VYNE Therapeutics’ Phase 2b trial of Repibresib gel for nonsegmental vitiligo failed to meet its primary endpoint of F-VASI50 (Facial Vitiligo Area Scoring Index 50% improvement) at week 24. The key secondary endpoint of F-VASI75 was also missed. While the highest dose (3%) showed nominally significant improvement in percent change from baseline in both F-VASI and T-VASI (Total VASI) scores at week 24, the company is terminating the trial’s extension phase and seeking an external partner for further development.
This setback highlights the challenges in developing topical therapies for vitiligo, a complex autoimmune disorder with a significant unmet need. The high placebo response observed in the vehicle arm, coupled with higher dropout rates in the active treatment arms (36.6% for Repibresib, 3% versus 10.6% for vehicle), raises questions about the trial design and the drug’s perceived benefit-risk profile by patients. The most common adverse events were application site pain and other cutaneous reactions, though mostly mild and resolving during the study. This raises the question of whether the observed efficacy, even if statistically significant in some measures, outweighs the treatment burden for patients.
VYNE’s decision to seek a partner suggests a strategic shift away from direct investment in Repibresib. This may be driven by the need to conserve resources given the trial’s negative outcome and the company’s reported cash position of $39.6 million as of June 30, 2025. This move allows VYNE to focus on its oral BET inhibitor, VYN202, potentially a more commercially viable approach for chronic inflammatory and immune-mediated conditions. Outsourcing Repibresib’s development also mitigates further financial risk for VYNE while allowing for potential future revenue streams should a partner successfully advance the drug.
This trial failure impacts the broader vitiligo landscape by slowing the progress of a potentially promising therapeutic mechanism. The high placebo effect underscores the difficulty in conducting vitiligo trials and the need for more robust endpoint measures and potentially longer observation periods. It also highlights the challenge of managing patient expectations and adherence in trials for conditions with visible manifestations, where even minor improvements in the control group can influence perceptions of efficacy.
Looking ahead, the full data analysis from this Phase 2b trial will be crucial for understanding the drivers behind the high placebo response and the elevated dropout rates in the treatment arms. This information will be essential for any potential partner considering further development of Repibresib. It also raises broader questions for the field about trial design in vitiligo, including patient selection, endpoint selection, and strategies to minimize placebo effects. Furthermore, VYNE’s experience underscores the growing pressure on smaller biotech companies to balance internal development with external partnerships, particularly in challenging therapeutic areas like vitiligo.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
