UPDATED [8/12/16] The U.S. Food and Drug Administration, with information received from the European Medicines Agency (EMA) and the French national medicines agency (ANSM), has completed a comprehensive review of safety information relevant to the investigational new drug BIA 10-2474 and the potential implications for related drugs under investigation in the U.S. The Agency has found, based on the available information, that BIA 10-2474 exhibits a unique toxicity that does not extend to other drugs in the class, called fatty acid amide hydrolase (FAAH) inhibitors.

There are no clinical trials with BIA 10-2474 underway in the U.S. The first phase 1 clinical trial of BIA 10-2474 was conducted in France in January, 2016, and resulted in the death of one enrolled subject and hospitalization of 5 others. Four of these 5 subjects experienced neurological injury.

Based on these findings, the FDA is working with sponsors to establish the appropriate path forward for FAAH inhibitors under investigation in the U.S. We are also working to ensure healthy subjects, patients, and investigators participating in FAAH inhibitor clinical trials are fully informed of the risks and potential benefits of these experimental therapies.

[1/22/16] FDA works with regulatory partners to understand French-based Biotrial phase 1 clinical study

The U.S. Food and Drug Administration is conferring with European regulators after a phase 1 clinical study, conducted by French clinical research organization Biotrial, resulted this week in the death of one enrolled subject and neurological injury to four others.

The study had focused on BIA 10-2474, an investigational new drug (IND) manufactured by Portuguese company Bial. Although no clinical studies with BIA 10-2474 have occurred in the U.S., FDA is conferring with the European Medicines Agency (EMA) and the French national medicines agency (ASNM). French authorities continue to investigate the events reported by Biotrial. FDA will learn as much as possible about BIA 10-2474 and the results of the French phase 1 study.

To meet FDA regulatory requirements, study sponsors collect rigorous laboratory and animal data and must submit such safety data to FDA in an IND application before any human volunteers may be enrolled in a phase 1 study. Furthermore, sponsors may not initiate phase 1 studies until 30 days after submitting an IND application to the agency. This period of time allows FDA scientists to review the safety data and determine if the proposed study is reasonably safe to proceed. If FDA determines that human subjects might be exposed unnecessarily to risk of illness or injury, the study may be placed on “clinical hold” by the agency. Catastrophic adverse events in phase 1 studies conducted in the U.S. are extremely rare.

BIA 10-2474 is reported to be an inhibitor of fatty acid amide hydrolase (FAAH), an enzyme involved in cell function in the nervous system. FAAH inhibitors have been studied for their potential therapeutic use in a number of neurological disorders. This week’s tragedy in France is the first human fatality following exposure to an FAAH inhibitor.

FDA is in the process of collecting and reviewing safety information pertinent to FAAH inhibitors under investigation in the U.S. FDA will work with sponsors to ensure the safety of participants in clinical studies and take regulatory action as appropriate. FDA will also work with sponsors to ensure patients and investigators participating in clinical studies of FAAH inhibitors are fully informed regarding the risks and potential benefits of these drugs.