According to a story from BioSpace, the current standard approaches for drug development aren’t well suited for rare diseases, which have unique characteristics in comparison to more widespread illnesses. As a result, Peter Marks, of the US Food and Drug Administration (FDA) Center for Biologics Evaluation and Research, argued for greater flexibility when evaluating possible treatments for them, such as gene therapies. Marks pushed for a single-arm, non-randomized trial approach during a recent panel conversation.
“There are many rare diseases affecting dozens to a few hundred individuals in the United States where the concept of trying to do a randomized trial is very challenging at best and impossible at worst.” – Peter Marks, director, Center for Biologics Evaluation and Research, FDA
With such small pools of patients, many might hesitate to get involved in a randomized trial, and in other cases, only smaller trials are possible. There is no single established approach for gene therapy trials, which are typically developed for rare genetic disorders.
Genetic medicine consultant and former biotech CMO Suyash Prasad believes that a single arm trial would be most effective in a non-heterogenous patient population, with a biological or mechanistic endpoint, a consistent pattern of disease progression, and substantial efficacy in a meaningful number of the patient population:
“If you have a subtle improvement, if you see only the improvement in one or two endpoints . . . if there’s a very heterogeneous disease population, then it becomes much harder to run a single-arm study.” – Suyash Prasad
Marks largely agreed with this; a treatment evaluated in such a trial would need to have a more significant effect in order to render a control group moot.
Accelerated Approval protocol is likely to play a role in this area of therapy development going forward, in which surrogate endpoints (based on biomarkers) that suggest clinical improvement can be used to approve a therapy more rapidly, with further confirmatory trials taking place later on. However, the pacing of these trials is important, with some experts, such as Holly Fernandez Lynch, calling for trials to already to be underway when Accelerated Approval is granted.
Future approaches could involve a trial design with both biomarker endpoints and clinical endpoints.
