- One-third of the drugs granted an accelerated approval from the Food and Drug Administration haven’t completed trials to confirm their potential benefits, an internal government watchdog reported Thursday in a report that highlighted the flaws in the 30-year-old program meant to speed new medicines for rare and deadly diseases to market.
- Of those that haven’t finished confirmatory trials, one-third are now past their originally planned completion date, leaving regulators, physicians and patients unsure of whether those medicines are effective, the report said. Among the biggest culprits for the delays are changes in standard of care and drug ownership.
- The report from the U.S. Department of Health and Human Services’ inspector general’s office was published just as Congress is preparing to approve legislation to renew the user fee program that funds a large portion of the FDA’s drug review activities. Some lawmakers had sought to set deadlines for confirmatory trials and strengthen FDA’s power to withdraw drugs, but the current bill doesn’t contain those measures.
The accelerated approval program was implemented as the U.S. grappled with the HIV crisis and was searching for a way to get medicines for the deadly infection to market more quickly. But its use has skyrocketed in recent years, with 70 of the 278 speedy approvals awarded by the FDA occurring in 2020 and 2021 alone.
The FDA awards those clearances on “surrogate endpoints,” or biological data that researchers believe can predict benefits that take longer to assess. The agency requires drugmakers to conduct follow-up trials that are meant to confirm those benefits.
Yet those trials haven’t always been completed on schedule, or sometimes not at all, the inspector general’s office reported. Of the total number of accelerated approvals granted, 104 have incomplete confirmatory trials. And while many of those incomplete trials are for recently approved drugs, 35 have have gone beyond their planned completion date.
Among the late trials was one for AMAG Pharmaceuticals’ premature birth drug Makena, a study that was completed in 2019 but was 64 months overdue. Next month, an FDA advisory committee will meet to discuss whether to pull Makena from the market because its benefits weren't confirmed in that study.
Those types of advisory committees have helped influence the fate of other drugs. Last year, for instance, drugmakers withdrew multiple immunotherapies in certain indications after negative votes from a panel of cancer experts reviewing their “dangling” accelerated approvals.
One advocacy group said the report’s findings show the accelerated approval program is in need of reform.
“The [inspector general] report confirms what has already been widely known: Pharmaceutical companies often fail to complete FDA-mandated post-market studies after a drug product is approved under the accelerated approval pathway,” Michael Carome, director of Public Citizen’s health research group, wrote in an email. “Congress needs to given FDA the authority to quickly withdraw accelerated approval when companies fail to meet their obligations to conduct post-approval studies.”
The changes Carome is pushing for won’t come immediately. Renewal of the FDA’s user fee program, which will expire Friday, is often an opportunity to alter the way the agency operates. However, a stopgap government funding bill that has passed the Senate and due to face a House of Representatives vote on Friday would renew the program for five years without changing the accelerated approval program.
The inspector general’s report was triggered, in part, by the FDA’s decision to grant an accelerated approval to Biogen’s Alzheimer’s drug Aduhelm. The FDA cleared Aduhelm because of its ability to clear up amyloid plaques in the brain, but overruled its expert advisers, who weren’t persuaded by the drug’s conflicting data.