Managing Scientist Exponent New York, New York, United States
Background: The Accelerated Approval Pathway enables the United States Food and Drug Administration (FDA) to expedite drug approvals for serious conditions with unmet medical need, using surrogate endpoints that predict clinical benefit, ensuring faster patient access. Since these drugs have limited long-term efficacy and safety data, the FDA often mandates Postmarketing Requirements (PMRs) to confirm benefit and assess risk. If additional studies or trials fail to show clinical benefit or reveal risks associated with long-term use, approval may be withdrawn.
Objectives: To evaluate PMRs for drugs approved under the Accelerated Approval Pathway, focusing on their status, study or trial design, therapeutic area, PMR timeline, and regulatory designation to assess trends and regulatory outcomes.
Methods: The FDA database of information on all postmarketing studies and clinical trials for drugs and biological products was downloaded and analyzed in Microsoft Excel to characterize the Center for Drug Evaluation and Research (CDER) PMRs specifically for drugs approved through the Accelerated Approval Pathway between 2020 and 2024. Only New Drug Applications and original submissions were included in the review, excluding Biologics License Applications and supplemental submissions. Drug indication and regulatory designation were obtained from Drugs@FDA: FDA-Approved Drugs Database, which provides FDA approved drug product labeling and approval history. ClinicalTrials.gov was used to track ongoing postmarketing trial status.
Results: Between 2020 and 2024, a total of 40 Postmarketing Requirements (PMRs) were issued for 28 drugs originally approved through the Accelerated Approval Pathway. All of these were classified as PMRs rather than Postmarketing Commitments (PMCs). Among them, 42.5% remained ongoing, 27.5% were pending, 12.5% were released, 10% were fulfilled, and 7.5% were submitted. The majority of these PMRs were for drugs with oncology indications, while a smaller proportion were for drugs treating rare and genetic diseases, liver disorders, and kidney disorders. The time elapsed between the original application approval date and the final report due date ranged from 12 to 116 months, with an average of 55 months, highlighting the variability in regulatory timelines for confirmatory studies and trials.
Conclusions: Most PMRs for Accelerated Approval drugs remain ongoing or pending, highlighting delays in confirmatory studies. While most PMRs pertain to drugs with oncology indications, extended timelines across therapeutic areas emphasize the need for timelier completion to ensure clinical benefit.
