FDA Halts Vyne Therapeutics' Psoriasis Trial Due to Safety Concerns

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on Vyne Therapeutics' Phase Ib trial of VYN202, an experimental BET inhibitor for plaque psoriasis. This decision comes after recent observations of testicular toxicity in dogs during a non-clinical toxicology study, causing a significant setback for the company's developmental pipeline.

Clinical Trial Suspension and Market Impact

Vyne Therapeutics announced on Friday that it has suspended all screening, enrollment, and dosing of patients in the early-stage trial of VYN202. The company's stock price tumbled 28% in pre-market trading, dropping from $1.88 to $1.35 per share following the news.

David Domzalski, CEO of Vyne Therapeutics, expressed disappointment but emphasized the company's commitment to patient safety. "We are disappointed by this unexpected development," Domzalski stated, adding that the biotech's top priority is the safety of its trial participants.

VYN202: A Selective BET Inhibitor

VYN202 is an oral medication designed to selectively target the BD2 domain of BET proteins, which play a crucial role in regulating genes involved in inflammation and oncogenesis. This selective approach was intended to optimize the benefit-risk profile for autoimmune diseases, potentially offering advantages over broader-acting BET inhibitors.

Prior to the clinical hold, Vyne had positioned VYN202 as a promising candidate for moderate-to-severe plaque psoriasis and rheumatoid arthritis. The company's strategy aimed to develop a safer and more tolerable BET inhibitor by focusing on BD2 selectivity, based on evidence that BD2 regulates gene expression of pro-inflammatory mediators while BD1 modulates cell-cycling and homeostatic functions.

Implications for Vyne's Pipeline and Industry Trends

While the VYN202 trial has been halted, Vyne clarified that its ongoing Phase IIb study of repibresib gel for vitiligo remains unaffected. Repibresib, a topical pan-BD BET inhibitor, is described by the company as "a distinct and unique compound from VYN202." Vyne expects to release topline Phase IIb data for repibresib by mid-year.

This setback for Vyne occurs amidst a busy week in the immunology and inflammation space. Recent developments include the debut of Swiss startup Granite Bio with $100 million in funding for autoimmune disease therapies, and a $765 million deal between Genentech and Flagship Pioneering's Repertoire Immune Medicines to develop T cell-targeting therapies.

The clinical hold on VYN202 also echoes previous challenges in the field, reminiscent of Gilead Sciences and Galapagos' experience with filgotinib, where testicular toxicity concerns led to regulatory restrictions and ultimately a rejection for rheumatoid arthritis approval in 2020.

As Vyne Therapeutics works with the FDA to resolve the safety issue and determine next steps for VYN202, the incident underscores the ongoing challenges in developing novel treatments for autoimmune diseases and the critical importance of safety evaluations in drug development.