FDA's accelerated approval reforms sneak into Congress' last-minute spending bill

When Robert Califf, M.D., retook the helm of the FDA earlier this year, reforming the accelerated approval pathway for new drugs was one of his top priorities.

Fast forward almost a year and those reforms are close to being cemented into law after they slid through negotiations to make the latest draft of Congress’ annual spending bill, which was unveiled Tuesday morning. If passed, the bill would codify more power for the FDA, namely giving the agency the power to request that confirmatory trials are initiated before a company receives accelerated approval. Once a company does receive an accelerated approval, it will be required to provide confirmatory trial status reports to the FDA every six months. 

The reforms are intended to shore up an often-relied-on mechanism for companies to take potentially beneficial drugs and get them into the hands of patients with little to no treatment options. Accelerated approval allows therapies to be approved based on evidence that they are reasonably likely to predict clinical benefit, rather than more straightforward efficacy data. Companies must then perform confirmatory studies to prove benefits. The pathway was opened in the 90s to spur the development of HIV treatments, but in the last decade has been primarily used to advance cancer therapies.

The omnibus bill also creates an accelerated approval oversight council, with members across the FDA including representatives from the Oncology Center for Excellence, Centers for Biologics Evaluation and Research and Center for Drug Evaluation and Research. 

Amending the accelerated approval pathway has been top of mind for Califf since he joined the agency in February, citing a need to shore up a process that remains critical to patients with few therapeutic options but that lacked dogged oversight. Companies using the pathway are able to make their case using surrogate data rather than evidence of clinical benefit, on the condition that the company confirms clinical benefit in a follow-up confirmatory trial.

But those trials often take years to complete while the drug is on the market and success is infrequent. One review found that between 1992 and 2017, only one in five accelerated meds had a survival benefit for patients in follow-up studies. In an interview with Fierce Biotech in April, Califf said the process had to be simplified to make it easier for companies to complete the follow-up work while verifying the efficacy of a product. 

“[W]e've got to do a better job of getting the post-market data,” he said. “And it ought to be easier to do the right thing for companies, easier to get the follow-up data than to not get it." 

While cancer drugs have dominated use of the pathway as of late, it's recently been used to expedite the availability of treatments for neurodegenerative and rare diseases. Biogen received accelerated approval for its Alzheimer's treatment Aduhelm in 2021, a controversial decision that ran contrary to the FDA's own advisers. And earlier this year, Novartis received an accelerated nod for its PIK3CA-related overgrowth spectrum treatment, Vijoice. Lawmakers specifically spelled out in the bill that at least one member of the review committee must come from the FDA’s Office of Neuroscience. 

The trillion-dollar bill is a last shot at landing a bipartisan proposal for funding the government before a new Congress takes shape next year. With Republicans set to take the gavel in the House of Representatives, Democrats were eager to avoid the threat of a government shutdown. Congress now has until midnight on Friday to push the bill through the legislative conveyer belt before federal funds run dry. 

Editor's note: This story was corrected to reflect that Amylyx received full FDA approval for its ALS treatment, not accelerated approval. The treatment's reference in the story has been removed and replaced with Novartis' Vijoice.