Clinical hold on studies of zelnecirnon (RPT193) in atopic dermatitis and asthma

The company expects to receive a formal clinical hold letter from the FDA.

The clinical hold determination was based on a serious adverse event of liver failure in one patient in the atopic dermatitis trial, the cause of which is currently unknown but which has been characterized as potentially related to zelnecirnon. Dosing of zelnecirnon has been halted in both clinical trials, as has enrollment of new trial participants. The clinical hold does not apply to RAPT’s ongoing trial of tivumecirnon (FLX475) in oncology.

A total of approximately 350 patients have been enrolled across three trials evaluating zelnecirnon - the two Phase II trials and an earlier Phase 1a/1b study. No evidence of liver toxicity has been observed with any other trial participant. Additionally, no evidence of liver toxicity was observed in nonclinical studies.

RAPT is undertaking a thorough investigation of this case, which involved a patient with a complex medical history, including a history of drug allergy to dupilumab, autoimmune disease resulting in thyroid hormone replacement therapy and use of an herbal supplement known to be associated with liver failure, as well as a reported COVID-19 infection during the time of the event.

“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.”