Cancer drugmakers pursuing FDA’s accelerated approval mechanism to sell their treatments more quickly should opt for randomized controlled trials instead of giving the experimental therapy to everyone.
The Food and Drug Administration announced Friday draft guidance on clinical trial considerations to support accelerated approval of oncology therapeutics.
Accelerated approval has come to the forefront after the controversy behind the approval of Biogen’s Alzheimer’s drug Aduhelm, but the cancer drug development space uses this mechanism most frequently. A JAMA Oncology study found 48 of the 66 oncology drugs approved between 2009 and 2022 came through the accelerated approval pathway.
Accelerated approval allows drugs treating an unmet medical need to reach patients more quickly by relying on a laboratory marker, or surrogate endpoint, that predicts a patient will benefit from taking it, instead of proving it definitively. Tumor shrinkage is a surrogate for survival, for example.
In the notice announcing the draft guidance, the FDA acknowledged cancer drug developers commonly use what’s called a single-arm trial when using accelerated approval. Single arm trials are a way to design the study so everyone receives the investigational therapy, instead of randomly assigning them to one group. Researchers typically use them in smaller studies to determine if the experimental drugs work well enough to move onto larger randomized trials.
But the FDA said the single-arm trials come with limitations including response rates that may not reasonably predict clinical benefit and small safety data sets. The agency prefers randomized controlled trials which are generally considered the gold standard.
“When properly designed and executed, a randomized controlled trial provides a more robust efficacy and safety assessment and allows for direct comparisons to a concurrent control arm.
Richard Pazdur, director of the FDA’s Oncology Center of Excellence, said the single-arm situation usually arises if a company “may not be adequately capitalized” and “wants to get their foot in the door, so to speak, with a single-arm study of a very limited number of patients.”
“That puts the patient at risk here,” Pazdur said at a Friends of Cancer Research meeting in November. “There is a period of vulnerability that we have to control and that period of vulnerability is between the time of the accelerated approval—if it is granted—and the confirmation or lack of confirmation of a clinical benefit in the confirmatory study. And we should try to reduce that period of vulnerability as much as possible.”
Drug sponsors can opt for what the agency called a “one trial approach,” in which they conduct a single randomized controlled trial to support an accelerated approval and to verify clinical benefit, FDA said in announcing the draft guidance. “The ‘one-trial’ approach maintains efficiency in drug development by providing early access to an investigational drug using the accelerated approval.”
To contact the reporter on this story: Jeannie Baumann in Washington at jbaumann@bloombergindustry.com
To contact the editor responsible for this story: Cheryl Saenz at csaenz@bloombergindustry.com
