Postmarketing requirements for drugs approved by the Food and Drug Administration for the treatment of solid tumor cancers, 2010-2019.

person Yolaine Jeune-Smith Cardinal Health, Dublin, OH info_outline Yolaine Jeune-Smith, Marjorie E. Zettler, Stephanie Fortier, Skyler Rupard, Ajeet Gajra, Bruce A. Feinberg

Authors person Yolaine Jeune-Smith Cardinal Health, Dublin, OH info_outline Yolaine Jeune-Smith, Marjorie E. Zettler, Stephanie Fortier, Skyler Rupard, Ajeet Gajra, Bruce A. Feinberg Organizations Cardinal Health, Dublin, OH Abstract Disclosures Research Funding Other Cardinal Health Background: In recent years, efforts to improve the efficiency and speed of drug development and approval have driven a surge of Food and Drug Administration (FDA) approvals for cancer drugs. For many cancer therapies, the serious or life-threatening nature of the condition and unmet medical need confers eligibility for expedited programs. Many cancers are also rare diseases, and the increasing use of precision medicine principles to define cancer types further contributes to smaller trial sizes. With limited clinical evidence at the time of approval, cancer drugs may be subject to a greater burden of postmarketing requirements (PMRs). We analyzed PMRs for solid tumor therapies approved by the FDA over the past decade. Methods: The FDA’s novel drug approvals (2010-2019) were reviewed to identify drugs receiving primary approval for solid tumor indications. Approval letters were accessed via the Drugs@FDA database and analyzed for PMRs required under accelerated approval (AA), the Pediatric Research Equity Act (PREA) and the FDA Amendments Act of 2007 Section 505(o) (505(o)). Data are presented using descriptive statistics. Results: A total of 60 drugs received primary approval from the FDA for solid tumor indications between 2010 and 2019 (20 [33.3%] received AA, 33 [55.0%] received orphan designation, and 45 [75.0%] received Fast Track or Breakthrough Therapy designation). The proportion of drugs receiving AA doubled between the period 2010-2014 and 2015-2019 (Table). Of the 60 drugs approved, 52 (86.7%) received a total of 180 PMRs. All 20 drugs approved under AA received PMRs, with a total of 25 PMRs issued under AA. Data from new clinical trials were required for 22 (88.0%) of the 25 PMRs. No PMRs were issued under PREA. Additional safety data required under 505(o) comprised the largest proportion of PMRs; 155 total PMRs (86.1% of all PMRs) were issued for 45 (75.0%) of the drug approvals. Pharmacokinetic or other clinical safety data were required for 96 (61.9%) of the 155 PMRs. Conclusions: More than three-quarters of the cancer drugs approved for the treatment of solid tumors in the past 10 years were issued PMRs, with the majority requiring new safety data. The results of this study indicate that PMRs represent a critical mechanism by which FDA collects safety and efficacy for solid tumor therapies, and underscore the importance of PMR fulfillment. Post-marketing requirements (PMRs) for solid tumor drugs approved 2010-2019. 2010-2014 (n, %) 2015-2019 (n, %) Total (n, %) Number of primary approvals for solid tumor drugs 24 36 60 Accelerated approval 5 (20.8%) 15 (41.7%) 20 (33.3%) Traditional approval 19 (79.2%) 21 (58.3%) 40 (66.7%) Approvals receiving PMRs 22 (91.7%) 30 (83.8%) 52 (86.7%) Total number of PMRs 102 78 180 Accelerated approval 7 (6.9%) 18 (23.1%) 25 (13.9%) Pediatric Research Equity Act 0 (0.0%) 0 (0.0%) 0 (0.0%) Section 505(o) 95 (93.1%) 60 (76.9%) 155 (86.1%)