Modernising the US FDA's Accelerated Approval pathway.

On Dec 29, 2022, US President Joe Biden signed The Consolidated Appropriations Act into law. This wide-reaching Act contains notable reforms to the US Food and Drug Administration (FDA) statutory and regulatory frameworks. The legislation amends key regulatory frameworks, including changes to the FDA-expedited approval programme, Accelerated Approval. 1 Department of Health and Human ServicesConsolidated Appropriations Act, Division FF–Health and Human Services, title III–Food and Drug Administration, section 3210. https://www.appropriations.senate.gov/imo/media/doc/JRQ121922.PDFDate: 2023 Date accessed: January 10, 2023 Google Scholar This pathway has been substantial for drug development globally since its introduction in 1992, permitting early regulatory approval based on surrogate endpoints likely to predict clinical benefit for drugs treating serious or life-threatening conditions. 2 Fashoyin-Aje LA Mehta GU Beaver JA Pazdur R The on- and off-ramps of oncology Accelerated Approval. N Engl J Med. 2022; 387: 1439-1442 Crossref PubMed Scopus (22) Google Scholar A further confirmatory study is typically required to validate true clinical benefit to permit conversion to standard approval, or in the case of a negative result, potentially medicine withdrawal. Recent scrutiny of the Accelerated Approval pathway, particularly after the approval of aducanumab for Alzheimer's disease, and the notable withdrawal of several cancer medicines (eg, bevacizumab in breast cancer), has led many to call for urgent reform of this pathway. 3 Lythgoe MP Jenei K Prasad V Regulatory decisions diverge over aducanumab for Alzheimer's disease. BMJ. 2022; 376e069780 Google Scholar , 4 US Food and Drug AdministrationWithdrawn cancer Accelerated Approvals. https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-cancer-accelerated-approvalsDate: June 12, 2022 Date accessed: January 10, 2023 Google Scholar As Accelerated Approval is predominately used in oncology, with cancer drugs accounting for 85% of use over the past decade, reforms are highly relevant for new cancer drug development and approval. 2 Fashoyin-Aje LA Mehta GU Beaver JA Pazdur R The on- and off-ramps of oncology Accelerated Approval. N Engl J Med. 2022; 387: 1439-1442 Crossref PubMed Scopus (22) Google Scholar We will therefore highlight key reforms, and potential opportunities and challenges these could present.