FDA Halts Vyne Therapeutics' Psoriasis Trial Due to Toxicity Concerns

The U.S. Food and Drug Administration (FDA) has imposed a clinical hold on Vyne Therapeutics' phase 1b trial for its novel BET inhibitor, VYN202, in plaque psoriasis patients. This decision comes after reports of testicular toxicity emerged in dogs during a non-clinical toxicology study, raising significant safety concerns for the experimental treatment.

BET Inhibitor Development Hits Roadblock

Vyne Therapeutics, a company at the forefront of developing selective BET inhibitors, designed VYN202 to target the BD2 portion of the protein. This approach was intended to mitigate the hematologic and gastrointestinal adverse effects typically associated with BET inhibitors in cancer treatment. The company's strategy focused on regulating gene expression of pro-inflammatory mediators while avoiding interference with cell-cycling and homeostatic functions.

Despite promising phase 1a data released late last year, which supported the company's hypothesis, the FDA's intervention has brought the phase 1b trial to an abrupt halt. Vyne has ceased all screening, enrollment, and dosing activities in response to the clinical hold.

Market Impact and Company Response

The news of the clinical hold had an immediate impact on Vyne Therapeutics' stock, with shares plummeting 20% to $1.50 in premarket trading. The company has stated that no patients in the current study have experienced serious adverse events related to VYN202.

David Domzalski, CEO of Vyne Therapeutics, addressed the situation, emphasizing the company's commitment to patient safety and their intent to work closely with the FDA to resolve the clinical hold. Prior to this setback, Domzalski had expressed optimism about the program's potential, stating at a recent investor event, "Assuming we do that [achieve a clean safety profile], I think the optionality for this product is quite substantial."

Broader Implications for BET Inhibitor Research

The clinical hold on VYN202 highlights the ongoing challenges in developing safer alternatives within the BET inhibitor class. This setback echoes previous issues in the field, such as Gilead Sciences and Galapagos' experience with filgotinib, where testicular toxicity concerns led to FDA restrictions and ultimately a rejection for rheumatoid arthritis approval in 2020.

While the VYN202 trial faces uncertainty, Vyne Therapeutics' phase 2b trial of repibresib, a topical pan-BD BET inhibitor for nonsegmental vitiligo, remains unaffected by the clinical hold. The company maintains that the topical delivery format of repibresib circumvents the safety concerns associated with systemic use of pan-BD BET inhibitors.

As the pharmaceutical industry continues to explore the potential of BET inhibitors, this development serves as a reminder of the complex balance between efficacy and safety in drug development, particularly in the realm of novel therapeutic approaches.