Is the accelerator working? An updated empirical analysis of FDA accelerated approvals.

e23025 Background: Since 1992, accelerated approval (AA) has become the most common pathway for initial approval of cancer drugs. AA relies on early phase studies that use surrogate endpoints, which arrive sooner. Hence, earlier approval can be beneficial for effective drugs but increases the risk that drugs without clinical benefit enter the market. This study aims to analyze the duration from enrollment to approval for the accelerated approval pathway versus regular approval. Methods: This is a retrospective cross-sectional study that analyses of all original and updated clinical trials that led to FDA accelerated or regular approval of cancer-specific drugs from 2022 through 2024. Eligible approvals were identified through FDA notifications. Clinical trials relevant to each approval indication were identified through the corresponding package insert. Total study duration and time from first enrollment to data cutoff were the primary study outcomes. Univariate linear regression was utilized to assess outcomes and results were stratified by primary tumor type, phase of trial that led to approval, and type of drug approved. Results: In total, 142 distinct indications among 136 drugs approved for treatment of solid and hematologic malignant neoplasms were identified from 2022 through 2024. Of the 136 drugs approved, 35 received AA and 101 received regular approval. Studies receiving AA required on average 250 fewer patients per trial to report a difference in primary outcome (p<0.001). Drugs receiving AA required on average 77 more months (6.4 years) to reach data cutoff from first patient enrollment than those receiving regular approval (p=0.028). When utilizing surrogate endpoints, drugs receiving AA reached data cutoff in an average of 122 months while drugs receiving regular approval reached data cutoff in an average of 45 months (difference of 76 months, p=0.059). While not statistically significant, it was noted that AA approvals took 62 fewer months to reach approval from data cutoff. Conclusions: Our findings suggest that, among clinical trials leading to FDA approval of cancer drugs from 2022 through 2024, use of surrogate endpoints was associated with a 20-day shorter length of study, and use of the AA pathway was associated with a 15 month longer total study duration. In the context of previous analyses suggesting shortened development time when utilizing the AA pathway, this reversal in recent approvals along with the greater uncertainty regarding the clinical benefit of surrogate endpoints deserves further scrutiny.