VYN201 for Vitiligo: Phase 1b Study Confirms Safety

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At Fall Clinical 2024 in Las Vegas, Nevada, from October 24 to 27, a poster was presented demonstrating the efficacy of the novel VYN201 treatment for active non-segmental vitiligo (aNSV)¹. These results come from a phase 1b clinical trial testing the use of VYN201 at various dosage levels. According to the study team at VYNE Therapeutics, these findings confirm the safety and tolerability of the topical gel for aNSV.

Background

VYN201 is a topical small molecule BET (bromodomain and extra-terminal domain) inhibitor that minimizes disease severity and encourages anti-inflammatory effects. Pre-clinical trials observed that the treatment inhibits CD8+ T-cell expansion without being cytotoxic and prevents detachment and melanin loss from the basal layers of tissue. Researchers saw a significant reduction in the release of MMP-9 (p < 0.001) and E-cadherin (p ≤ 0.01). These pre-evaluations were also presented through a poster at this year’s Fall Clinical.²

“VYN201 represents a differentiated potential treatment for aNSV, as it down-regulates vitiligo markers, up-regulates melanogenesis factors, prevents continued depigmentation in patients, and shows evidence of re-pigmentation,” the investigators noted.

Methods and Materials

The phase 1b, open-label, multi-center study took place over 16+ weeks with 28 days of screening, 112 days of outpatient treatment, and 7 days of safety follow-up. Patients were split into 3 dose cohorts of 0.5% (n = 10), 1% (n = 10), and 2% (n = 9). The topical treatment was applied once daily on affected skin not exceeding 10% of body surface area.

The 29 participants were between the ages of 18 and 75 and had been clinically diagnosed with aNSV for at least 1 month. Eligibility also included having a Facial Vitiligo Area and Severity Index Score (F-VASI) of ≥ 0.5 with active vitiligo on the face. Active lesions were defined as having hypochromic borders, confetti-like depigmentation, peri-lesional inflammation, and/or Koebner phenomenon.

Results

All 3 dosage cohorts had significant clinical response after 16 weeks of multiple-dose administration. Participants with the 0.5% dose experienced a -7.5% change in F-VASI scores while there was a -30.2% change in F-VASI for the 1% dosage group. Ultimately, the 2% dose group experienced the most drastic change in F-VASI score at -39.0%. The poster also featured patient photographs taken before and after treatment, including a participant with near-complete depigmentation.

Additionally, the mean scores of localized skin tolerance assessments (LSTA) did not increase over the course of the 16-week treatment. Although there were some mild to moderate adverse effects such as erythema, stinging, and dryness, no serious events occurred and none of these TEAEs led to treatment discontinuation. There were also no clinically relevant localized skin tolerability findings.

Conclusion 

Through this study, researchers confirmed that patients treated with VYN201 saw a significant dose-dependent clinical response by the 16-week mark. The topical delivery enabled local anti-inflammatory effects and minimized systemic exposure while maintaining a strong safety profile.

"This disease state has had marked, 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 with Dermatology Times. "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. We're looking forward to continuing the program and involving the dermatology community in the next steps for VYN201."³

References

1. 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.

2. 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.

3. Andrus E, Stuart I. VYN201 for vitiligo: promising data showcases potential of BET inhibition. Dermatology Times. May 22, 2024. Accessed November 1, 2024. https://www.dermatologytimes.com/view/vyn201-for-vitiligo-promising-data-showcases-potential-of-bet-inhibition