One hallmark of the FDA's accelerated approval pathway is the requirement that medicines prove their benefits in confirmatory trials. Now, new research shows that many cancer drugs approved under the pathway couldn't demonstrate survival benefits after five years.
The FDA’s accelerated approval pathway dates back to 1992, when it was first used to quickly roll out treatments to address the HIV/AIDS epidemic of the 1980s.
These days, more than 80% of all accelerated approvals are granted for oncology therapies, according to a recent study published in the Journal of the American Medical Association.
For the recent study, the team looked at the clinical benefits of certain oncology meds that secured accelerated approval and their subsequent performance in confirmatory studies.
The researchers examined 129 accelerated approvals from 2013 to 2023. Among those meds, 46 approved between 2013 and 2017 had more than five years of follow-up data available for review by the time of the study.
Out of that group, 63% of therapies were converted to a traditional approval even though less than half (43%) proved clinically beneficial in confirmatory trials.
Among the drugs that secured full approvals, 40% of the nods were based on overall survival benefits while 44% were based on progression-free survival results. One full approval, meanwhile, was granted despite a negative confirmatory trial, the study reported.
All in all, the study concluded "most" cancer drugs that were granted accelerated approval "did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval," the researchers wrote.
Still, the prominent industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA) was quick to defend the accelerated approval program. In a statement, a PhRMA spokesperson said the pathway has been “highly successful, providing timely access to treatments for HIV/AIDS, cancers and rare diseases, leading to better health outcomes for millions of patients."
Meanwhile, the FDA has recently expressed concern over extended timelines to conduct confirmatory studies and has urged companies to reduce the time to prove clinical benefit in order to minimize patient exposure to drugs that aren't effective.
In 2022, the agency was granted the authority to require companies to have necessary confirmatory trials already underway at the time of accelerated approvals.
This came into play just recently in March, when two of Regeneron’s applications for its CD20xCD3 bispecific odronextamab in certain blood cancers were rejected due to a lack of progress on said confirmatory trials.
However, the exact qualifications for a study to be considered underway are considered on a “case-by-case basis,” head of the FDA’s Oncology Center of Excellence Richard Pazdur, M.D., said at a recent oncology event.
The trials do have to be at least enrolling, however, meaning Regeneron’s studies at the safety lead-in phase didn’t count for its filings.