The FDA needs to strengthen guardrails to ensure its accelerated approval pathway is used appropriately, the HHS Office of Inspector General (OIG) said.
The agency should do two things, the OIG recommended in a new report: it should define when its intra-agency accelerated approval council should advise on certain drug applications, and it should ensure all meetings with drug companies are documented in its files.
The report was prompted by the FDA’s 2021 approval of the Alzheimer’s disease drug aducanumab (Aduhelm) using the accelerated approval pathway.
The aducanumab approval raised concerns in Congress and throughout the medical community about the accelerated pathway program and the agency’s judgment, the OIG said. It spurred a congressional investigation that demonstrated how the FDA broke with its own protocols by inappropriately collaborating with drugmaker Biogen on briefing documents and holding unreported meetings.
In light of this, the OIG examined the FDA’s decision-making process in a sample of 24 accelerated drug approvals.
Of the 24 drugs, three approvals deviated from the others — aducanumab; the synthetic hormone hydroxyprogesterone caproate (HPC; Makena), which was approved in 2011 to reduce the risk of recurrent preterm birth; and the Duchenne muscular dystrophy treatment eteplirsen (Exondys 51).
Two of these drugs are no longer on the market. In 2023, the FDA withdrew its approval of HPC after a years-long battle. In 2024, Biogen stopped selling aducanumab.
The FDA’s accelerated approval program was designed to speed the development and review of new drugs to treat serious and life-threatening conditions. Approval decisions are based on surrogate endpoints that are thought to predict clinical benefit. Drug companies are required to conduct confirmatory studies to verify these benefits, but that doesn’t always happen quickly.
“The three cases raised by the OIG report are all well-documented, concerning cases of what can go wrong with the accelerated approval pathway,” Benjamin Rome, MD, MPH, of Brigham and Women’s Hospital in Boston, told MedPage Today.
“Eteplirsen was granted approval in 2016 and after 9 years, the drug’s manufacturer still has not provided evidence that it improves outcomes for people with Duchenne muscular dystrophy,” Rome pointed out.
“The FDA has also approved newer treatments from the same company, including a gene therapy treatment, based on the same weak evidentiary standards,” he added. “And despite not knowing whether these drugs work, prices exceed $1 million a year, and we have spent $3 billion on these treatments from 2016-2022.”
The OIG review revealed that for 21 of the 24 drugs, the FDA followed a consistent approach with no formal scientific disputes or informal disagreements.
For the other three drugs — aducanumab, HPC, and eteplirsen — the FDA’s reviewers or its advisory committees raised significant concerns before the drug was approved. Disagreements about aducanumab and HPC were informal but concerns about eteplirsen escalated to a formal dispute.
For the eteplirsen and aducanumab approvals, the FDA made its decision using analyses not included in the drug companies’ original analysis plans, the OIG said. In addition, some meetings with Biogen about aducanumab appeared to be missing from the FDA’s administrative files, and others were not fully documented.
Of the two recommendations the OIG made, the FDA agreed with the second, but not the first. Requiring the accelerated approval council to evaluate specific drug applications would be inefficient, the agency said.
The FDA concurred, however, that ensuring all meetings with drug companies are documented is important.
“FDA has recently taken steps to clarify appropriate documentation of substantive communications between FDA and external entities, including by updating internal procedures,” the agency wrote in response to the OIG report. “FDA believes these existing processes are sufficient to ensure appropriate documentation moving forward, and we do not think additional steps are necessary at this time.”
Source link : https://www.medpagetoday.com/washington-watch/fdageneral/113802
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Publish date : 2025-01-16 17:59:38
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