The European Medicines Agency (EMA) is proposing a set of changes to its guidelines on how to reduce the risks of first-in-human trials. The agency says a rewrite is needed in part to incorporate lessons learnt from the tragic Phase I first-in-human trial of Bial's BIA 1-2474 earlier this year. One volunteer died and four volunteers were hospitalized owing to adverse effects of the fatty acid amide hydrolase (FAAH) inhibitor. A report by French drug safety regulators found that poor study design likely contributed, noting that doses were escalated too quickly and without taking into account pharmacokinetic data from previously dosed patients.

The EMA also notes that the current guidelines, written in 2007, focus on non-clinical aspects of drug development and single-ascending-dose trials. The EMA plans to update the guidelines to reflect increased use of 'integrated' trial designs that combine multiple substudies (analysing single and multiple ascending doses, food interactions, different age groups and early proof-of-concept end points) into a single first-in-human trial.

Comments on the proposal are due by 30 September 2016. A revised draft guideline is expected by the end of the year.

Separately, the US FDA concluded last month that BIA 1-2474 “exhibits a unique toxicity that does not extend to other drugs in the class”. The FDA is currently working with sponsors to establish an appropriate path for other FAAH inhibitors. This could be good news for Johnson & Johnson (J&J), who put its JNJ-42165279 on hold following Bial's Phase I disaster. J&J was testing its Phase II candidate for efficacy in generalized anxiety disorder and major depressive disorder. Pfizer and others have previously tested FAAH inhibitors for pain indications, but many of these companies dropped development of their candidates owing to limited efficacy before the Bial tragedy.