A Tightening of Regulations for Phase I Clinical Studies?
The Food and Drug Administration (FDA) has announced that they have launched a safety probe into fatty acid amide hydrolase (FAAH) inhibitors under investigation in the US. The investigation comes in the aftermath of a Phase I clinical trial in France, in which one healthy volunteer died while taking a drug of the FAAH class. A further 4 volunteers have been left with neurological damage. The drug, BIA 10-2474, was in development by Portuguese pharmaceutical company Bial, and being tested in a facility in Rennes, by French drug evaluation company Biotrial.
Accidents such as this are incredibly rare. The last high profile Phase I incident was a decade ago when volunteers participating in a trial at Northwick Park in the UK received a monoclonal antibody named TGN1412, leading to catastrophic system organ failure. One of the criticisms of that study was an unsuitable time interval between different individuals being given the drug, something that has been echoed by the UK Royal Statistical Society for the French trial.
The FDA probe will collect and review safety information on FAAH compounds currently in clinical trials. In France too, a number of investigations have been opened including by the French drug regulator (ANSM), the General Inspectorate of Social Affairs (IGAS) as well as the health division of the Paris Prosecutors Office. Regardless on the outcome of the investigations, the disaster will very likely lead to a tightening of requirements for first in man studies, in particular with respect to dose levels, dosing intervals and the need for more robust pre-clinical testing.
Both Pfizer and Sanofi have had FAAH compounds in development, neither of which exhibited safety signals. Janssen’s FAAH compound, JNJ-42165279, currently in Phase II for the treatment of major depressive disorder and anxious distress, may also be subject to increased regulatory scrutiny. Janssen have voluntarily suspended dosing in this Phase II study as a precautionary measure.