A Phase 1b clinical trial evaluating VYNE Therapeutics' VYN201, a topical small molecule BET (bromodomain and extra-terminal domain) inhibitor, has demonstrated promising results in patients with active non-segmental vitiligo (aNSV). The study, presented at Fall Clinical 2024, confirmed the safety and tolerability of VYN201 and showed a dose-dependent clinical response, suggesting its potential as a novel treatment for this challenging skin condition. The results offer hope for a new therapeutic avenue in vitiligo, an area with significant unmet medical needs.
VYN201 Mechanism and Preclinical Data
VYN201 works by inhibiting BET proteins, which play a role in inflammation and immune response. Preclinical trials showed that VYN201 inhibits CD8+ T-cell expansion without being cytotoxic and prevents detachment and melanin loss from the basal layers of tissue. Researchers observed a significant reduction in the release of MMP-9 (p < 0.001) and E-cadherin (p ≤ 0.01), further supporting its potential to mitigate vitiligo markers and promote melanogenesis.
Phase 1b Trial Design and Patient Population
The open-label, multi-center Phase 1b study enrolled 29 participants aged 18 to 75 with a clinical diagnosis of aNSV for at least 1 month and a Facial Vitiligo Area and Severity Index Score (F-VASI) of ≥ 0.5 with active vitiligo on the face. Patients were divided into three dose cohorts: 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 for 16 weeks.
Clinical Response and Safety Profile
After 16 weeks of treatment, all three dosage cohorts showed significant clinical improvement. The 0.5% dose group experienced a -7.5% change in F-VASI scores, while the 1% dosage group showed a -30.2% change. The 2% dose group had the most substantial change, with a -39.0% reduction in F-VASI score. Localized skin tolerance assessments (LSTA) remained stable throughout the treatment period. While some mild to moderate adverse effects like erythema, stinging, and dryness were reported, no serious adverse events occurred, and no patients discontinued treatment due to these effects.
Implications for Vitiligo Treatment
These findings suggest that VYN201 has the potential to address the significant unmet need for effective and well-tolerated treatments for vitiligo. "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," said Iain Stuart, PhD, the chief scientific officer at VYNE. The topical delivery of VYN201 enables local anti-inflammatory effects and minimizes systemic exposure, contributing to its favorable safety profile. VYNE Therapeutics is planning to continue the program and involve the dermatology community in further development of VYN201.
