ICER Calls for Enhanced Transparency in FDA's Accelerated Approval Pathway
核心洞察
The Institute for Clinical and Economic Review (搜索) (ICER) released a report recommending greater transparency in the FDA's accelerated approval pathway for drugs treating serious conditions with no approved treatments.
The report proposes implementing a scoring system for clinical trial quality, requiring advisory committees for reviews, and strengthening surrogate endpoint selection to improve pathway performance.
Recent accelerated approvals include Denali Therapeutics' Avlayah (搜索) for rare disease and Rocket Pharmaceuticals' gene therapy Kresladi, while controversial cases like Biogen's withdrawn Aduhelm highlight ongoing concerns about evidence standards.
The Institute for Clinical and Economic Review (搜索) (ICER), an influential drug pricing body, has called for increased transparency in the U.S. Food and Drug Administration's accelerated approval pathway, citing concerns about evidence standards and decision-making processes for drugs treating serious conditions with limited treatment options.
The accelerated approval pathway enables faster authorization of drugs for serious conditions with no approved treatments by utilizing surrogate endpoints—markers that predict clinical benefit without directly measuring it—significantly reducing the time required to obtain regulatory approval. However, manufacturers must still conduct confirmatory trials to verify the expected clinical benefit following approval.
Recent Approvals and Ongoing Controversies
This year's accelerated approvals include Denali Therapeutics' rare disease drug Avlayah (搜索) and Rocket Pharmaceuticals' gene therapy Kresladi for a childhood disorder. However, the pathway has faced scrutiny over safety and efficacy concerns, most notably with Biogen's Alzheimer's drug Aduhelm, which received controversial accelerated approval in 2021 without clear evidence of patient benefit. The drugmaker ultimately discontinued the treatment three years later.
"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 told Reuters.
ICER's Reform Recommendations
The ICER report outlines several policy options to enhance the accelerated approval pathway, including strengthening surrogate endpoint selection, mandating advisory committees for accelerated approval reviews, and improving decision-making transparency.
A key proposal involves implementing a scoring system for clinical trial and evidence quality. "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 stated.
Pricing and Access Reforms
The report also addresses economic considerations, recommending that coverage of accelerated approval drugs be linked to fair, value-based pricing with price updates as additional evidence emerges. It proposes limiting patient cost-sharing when no alternative treatments exist.
Additional recommendations include increasing enforcement requirements for completing confirmatory trials and conducting focused re-reviews by drug class or disease area, with priority given to those with the greatest evidence uncertainty.
Regulatory Context
The FDA issued new guidance last year to clarify clinical evidence requirements for accelerated approvals, specifically addressing the development of surrogate endpoints that are "reasonably likely" to predict clinical benefit. This guidance represents the agency's effort to balance expedited access to potentially life-saving treatments with appropriate evidence standards for patient safety and efficacy.