FDA Places Clinical Hold on RAPT Therapeutics' Zelnecirnon Trials Following Liver Failure Case

Key Insights

• The FDA has placed a clinical hold on RAPT Therapeutics' zelnecirnon (RPT193) trials for atopic dermatitis and asthma due to a serious adverse event.
• The adverse event was a case of liver failure in a patient participating in the atopic dermatitis trial, with potential links to zelnecirnon under investigation.
• RAPT Therapeutics has halted dosing and enrollment in the affected trials and is actively investigating the case, while the oncology trial remains unaffected.

RAPT Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on its trials evaluating zelnecirnon (RPT193) for the treatment of atopic dermatitis and asthma. The decision follows a report of liver failure in one patient participating in the atopic dermatitis trial. The company expects to receive a formal clinical hold letter from the FDA.

The specific case involved a patient with a complex medical history, including a drug allergy to dupilumab, autoimmune disease requiring thyroid hormone replacement therapy, use of an herbal supplement known to be associated with liver failure, and a reported COVID-19 infection around the time of the event. While the cause of the liver failure is currently unknown, it has been characterized as potentially related to zelnecirnon.

Trial Impact and Investigation

RAPT Therapeutics has halted the dosing of zelnecirnon and enrollment of new participants in both the atopic dermatitis and asthma clinical trials. However, the clinical hold does not extend to RAPT’s ongoing trial of tivumecirnon (FLX475) in oncology. Across the three trials evaluating zelnecirnon—two Phase II trials and an earlier Phase 1a/1b study—approximately 350 patients have been enrolled. Notably, no other trial participant has exhibited evidence of liver toxicity, and nonclinical studies also showed no signs of liver toxicity.

The company is undertaking a thorough investigation of the case. "This is an unfortunate and unexpected event, and we are working diligently to get more information on this case," said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. "Patient safety is our top priority and we will work with the FDA to resolve this as quickly as possible."

Zelnecirnon (RPT193)

Zelnecirnon is an oral small molecule CCR4 antagonist being developed for the treatment of atopic dermatitis and asthma. CCR4 is a chemokine receptor involved in the trafficking of immune cells, including Th2 cells, which play a key role in the pathogenesis of these inflammatory conditions.