Report Calls for More Scrutiny in FDA Drug Approvals

The U.S. Food and Drug Administration should be more transparent when granting accelerated approval for certain drugs, the Institute for Clinical and Economic Review (ICER), an influential drug pricing body, said in a report Thursday.

The FDA's accelerated approval pathway speeds up authorization of drugs for serious conditions with no approved treatments by using surrogate endpoints, markers that predict clinical benefit without directly measuring it, and significantly cutting the ‌time needed to win the regulator's approval.

However, manufacturers whose drugs are approved under the accelerated ​approval pathway must still conduct confirmatory trials to verify the expected clinical benefit.

Drugs that obtained accelerated approval this year include Denali Therapeutics' rare disease drug Avlayah ⁠and Rocket Pharmaceuticals' gene therapy Kresladi for a childhood disorder.

Expedited approval for drugs under the pathway has raised questions regarding the safety and efficacy of these treatments. For instance, in 2021, Biogen's Alzheimer's drug ⁠Aduhelm faced controversy over the FDA's accelerated approval without clear evidence of patient benefit. Three years later, the drugmaker dropped the treatment.

Some are concerned that tougher evidence standards mean fewer drugs are being approved under the pathway while others say too many ‌drugs are approved with weak evidence and without the required confirmatory follow-up, ICER CEO ​Sarah Emond said.

By ‌last year, the FDA had issued new guidance to clarify its position on clinical evidence requirements for accelerated approvals such as developing surrogate endpoints ‌that are "reasonably likely" to predict clinical benefit.

ICER's report recommends several policy options and checks to improve the accelerated approval pathway, such as strengthening the selection of surrogate endpoints, requiring advisory committees ⁠for accelerated approval reviews and improving transparency in ‌decision-making.

"A scoring system for clinical ⁠trial and evidence quality could allow FDA to track AA pathway performance over time and across study sponsors and might serve ⁠as an ⁠early warning system to identify trials at risk of delay or failing to provide the necessary data for conversion to full approval," the ‌report said.

It also recommended linking coverage of accelerated approval drugs to fair, value-based pricing, updating prices as more evidence emerges, and limiting patient cost-sharing when no alternative treatments exist.

Other proposals include increasing enforcement requirements to complete confirmatory ‌trials and conduct ​focused re-reviews by drug class or ‌disease area, prioritizing those with the most uncertainty in the evidence.

The National Pharmaceutical Council, a health policy research organization whose members include pharma giants Eli Lilly, Biogen and J&J, said ​that despite the challenges, "research shows the pathway is largely working as intended." It added that accelerated approvals deliver value to patients, with the overall benefits outweighing risks.