VYNE Completes Phase 2b Enrollment for Vitiligo Gel

Image Credit: © Rabizo Anatolii - stock.adobe.com

VYNE Therapeutics announced today the completion of enrollment in a phase 2b trial of repibresib (VYN201) gel for nonsegmental vitiligo. This milestone marks significant progress in developing a potential treatment for this autoimmune depigmenting disorder. Top-line results are anticipated in mid-2025, positioning repibresib as a promising therapeutic candidate for patients with vitiligo, where options remain limited.¹

“We are pleased to have recently completed enrollment in our phase 2b trial evaluating VYN201 for the treatment of vitiligo, which marks an important milestone for the program and reflects the continued strong execution of our clinical team,” said David Domzalski, president and chief executive officer of VYNE, in a news release. “We believe VYN201 gel has the potential to become a differentiated therapy for patients with vitiligo, and we look forward to reporting top-line data from this phase 2b trial in the middle of this year.”

Affecting approximately 0.5 to 2.0% of the global population, nonsegmental vitiligo represents the most common subtype of the condition. Despite its prevalence, there is only 1 FDA-approved therapy for vitiligo, underscoring the need for innovative treatments.

Study Design

According to the company, the phase 2b trial (NCT06493578) is a randomized, double-blind, vehicle-controlled study evaluating the efficacy, safety, and pharmacokinetics of once-daily repibresib gel in 3 concentrations (1%, 2%, and 3%) compared to vehicle. A total of approximately 180 participants with active or stable nonsegmental vitiligo have been enrolled, with equal randomization across treatment arms.

The trial's primary endpoint is the proportion of patients achieving a ≥50% improvement in the Facial Vitiligo Area Scoring Index (F-VASI50) at week 24. Secondary endpoints include broader F-VASI and Total VASI outcomes at weeks 24 and 52. Following the initial 24-week period, the company stated participants in the active treatment groups may extend therapy for 28 weeks, while those in the vehicle group will be re-randomized to active treatment.

Therapeutic Potential of Repibresib

Repibresib, a pan-bromodomain and extra-terminal domain (BET) inhibitor, represents a novel "soft" drug designed for localized application, minimizing systemic exposure while targeting inflammatory pathways. VYNE stated that preclinical studies have demonstrated its capacity to reduce inflammatory biomarkers and improve disease severity across multiple models. The gel formulation offers a differentiated approach for vitiligo management.

Conclusion

The phase 2b trial of repibresib gel signifies a step in addressing the unmet need for effective vitiligo treatments. If successful, repibresib could emerge as a transformative therapy for nonsegmental vitiligo, leveraging its targeted anti-inflammatory properties and low systemic exposure profile.

VYNE Therapeutics anticipates sharing top-line data from this pivotal trial in mid-2025, further advancing the therapeutic landscape for vitiligo.

Background

Early findings from preclinical studies and a phase 1b trial of repibresib demonstrated the treatment’s ability to minimize disease severity through anti-inflammatory mechanisms while supporting melanocyte recovery. In these studies, the therapy inhibited CD8+ T-cell expansion, reduced biomarkers like MMP-9 and E-cadherin, and showed significant re-pigmentation effects. Results from the phase 1b trial revealed a dose-dependent clinical response, with participants in the highest dose cohort (2%) achieving a 39% improvement in the F-VASI after 16 weeks of treatment.^2-3

Encouragingly, the company stated that repibresib has shown a rapid onset of action, addressing a major challenge in vitiligo management, where re-pigmentation often requires extended treatment durations. The gel formulation also provides localized therapeutic effects with minimal systemic exposure, contributing to a favorable safety profile.

"This disease state has had marked unmet need for many, many years. It has been overlooked by industry with respect to new therapies, and even the therapies that are coming through now are all based on one pharmacology," Iain Stuart, PhD, the chief scientific officer at VYNE said in an interview Dermatology Times at the time of initiation of the phase 2b trial. "We think that's unacceptable. We think the potential for BET inhibition could be very broad, and not just in vitiligo, but into all the dermatologic and immunologic diseases. The very fact that we have shown the very first clinical dataset in an autoimmune disease, and it happened to be vitiligo, was particularly encouraging."⁴

References

1. 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 January 6, 2025. https://vynetherapeutics.com/uncategorized/vyne-therapeutics-completes-enrollment-in-phase-2b-trial-evaluating-vyn201-for-the-treatment-of-nonsegmental-vitiligo/
2. Stuart I. Phase 1b: Translational evaluation of VYN201, a pan-BD BET inhibitor, for the treatment of non-segmental vitiligo. Poster presented at the 44th Annual Fall Clinical Dermatology Conference. Las Vegas, Nevada. October 24 to 27, 2024.
3. Stuart I. Preclinical studies: Translational evaluation of VYN201, a pan-BD BET inhibitor, for the treatment of non-segmental vitiligo. Poster presented at the 44th Annual Fall Clinical Dermatology Conference. Las Vegas, Nevada. October 24 to 27, 2024
4. Andrus E, Stuart I. VYN201 for vitiligo: promising data showcases potential of BET inhibition. Dermatology Times. May 22, 2024. Accessed January 6, 2025. https://www.dermatologytimes.com/view/vyn201-for-vitiligo-promising-data-showcases-potential-of-bet-inhibition