EMA Updates Advanced Therapy Guidelines for Developers
Sponsors developing medicines based on genetically modified cells, including CAR T-cells, should conduct exploratory trials to assess dose selection and timing of response to determine efficacy, according to updated guidance by the European Medicines Agency (EMA).
The guidelines, which include recommendations for clinical trials, will take effect on June 1. They replace guidance enacted in 2012, which was developed before the first gene therapy medicinal product using genetically modified cells was authorized.
EMA says dose selection studies should be conducted to examine safety, toxicity and anti-tumor activity at different dose levels, and to define the recommended dose or dose range for phase 2 trials. The agency added that conventional drug-drug interaction studies and renal/hepatic impairment studies are less likely to be applicable to CAR T-cells and should be considered on a case-by-case basis.
The agency says a randomized, controlled trial design is preferred, and comparison to best supportive care or investigator’s choice treatment is preferred to single-arm trials. EMA says it has received input from the FDA on the guidelines and is seeking alignment where possible.