Image Credit: © Axel Bueckert – stock.adobe.com
Key takeaways
- Repibresib missed both primary and key secondary endpoints in Phase IIb, but showed nominally significant improvements in percent F-VASI and T-VASI reduction at the highest dose.
- The trial’s interpretability was limited by an unusually strong vehicle response and high discontinuation rates in treatment arms—up to 36.6% in the 3% cohort.
- Despite trial termination, VYNE plans to explore partnerships and further development of its InhiBET BET inhibitor platform, including oral candidate VYN202.
VYNE Therapeutics has shared topline results from a Phase IIb clinical trial (NCT06493578) evaluating its Repibresib gel in nonsegmental vitiligo. The trial failed to 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
Secondary and exploratory findings highlight dose-related effects
Additionally, the trial did not achieve its key secondary endpoint of F-VASI75. However, nominally statistically significant effects were observed across other key secondary and exploratory endpoints.
- The highest dose group (Repibresib 3%) showed a nominally statistically significant improvement in percent change from baseline in F-VASI score at week 24 compared to vehicle.
- The F-VASI percent change from baseline at week 24 was -43.6% for Repibresib 3% versus -25.6% for vehicle.
- An exploratory analysis also showed a greater reduction in T-VASI score at week 24 for Repibresib 3% compared to vehicle.
- The percent change from baseline in T-VASI score at week 24 was -28.3% for Repibresib 3% versus -16.2% for vehicle.
VYNE cites vehicle response and dropout rate as trial challenges
According to VYNE, the company believes that these results were affected 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%). VYNE will discontinue treatment in the ongoing extension phase of this study and terminate the trial.
In a press release, David Domzalski, president and chief executive officer of VYNE, said: “We are disappointed with the results of our Phase IIb trial, which were impacted by an unexpectedly high treatment effect in the vehicle arm and a high discontinuation rate in the active arms. 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.”
Trial design and enrollment details
This Phase IIb trial was a randomized double-blind, vehicle-controlled, multi-center study that evaluated the safety and efficacy of Repibresib across 45 sites in North America.
- A total of 177 participants with nonsegmental vitiligo were included in the modified intent-to-treat population.
- Participants received once-daily topical Repibresib at concentrations of 1%, 2%, or 3%, or vehicle.
- Exploratory analyses evaluated percent change from baseline in T-VASI score at week 24.
Prior Phase Ib study showed dose-dependent improvements
In October 2023, VYNE shared positive results from Repibresib—then coined VYN201—in patients with nonsegmental vitiligo. A 16-week open-label Phase Ib trial demonstrated a statistically significant dose dependent reduction in F-VASI score from baseline for the VYN201 1.0% and 2.0% strengths cohorts compared to the 0.5% cohort. VYN201 was generally well tolerated with no clinically relevant treatment emergent adverse events observed across all doses.2
References
1. VYNE Therapeutics Announces Topline Results from Phase 2b Trial with Repibresib Gel in Nonsegmental Vitiligo. News release. July 30, 2025. Accessed July 30, 2025. https://vynetherapeutics.com/uncategorized/vyne-therapeutics-announces-topline-results-from-phase-2b-trial-with-repibresib-gel-in-nonsegmental-vitiligo/
2. VYNE Therapeutics Announces Positive Data from Phase 1b Trial for Novel BET Inhibitor VYN201 in Patients with Nonsegmental Vitiligo. News release. October 30, 2023. Accessed July 30, 2025. https://vynetherapeutics.com/press-releases/vyne-therapeutics-announces-positive-data-from-phase-1b-trial-for-novel-bet-inhibitor-vyn201-in-patients-with-nonsegmental-vitiligo/