Clinical development of new drugs for adults and children with cancer in 2010-2020: Longitudinal study of investigational drugs.

Abstract

1563 Background: Many investigational drugs start clinical testing to evaluate potential therapeutic benefits for oncology patients, but few eventually receive FDA approval. Moreover, only a small number is evaluated in pediatric populations, potentially contributing to the paucity of new approved drugs for young patients with cancer. Limited information is available on the development pipeline of investigational drugs, including the range of drug types entering clinical trials, trial phases at which development stalls, or rate of regulatory approval. To inform current clinical development efforts, we characterized the development and outcomes for a comprehensive sample of New Molecular Entities (NMEs) that started clinical testing worldwide in 2010-2015. Methods: We performed a longitudinal study using AdisInsight, a commercial database of global pharmaceutical research and development. This is a comprehensive database of drug development activity, which collects and curates data from trial registries, conference proceedings, journal publications, and press releases. Using these data, we identified all NMEs starting their first clinical trial for an oncology indication in 2010-2015. We followed each NME from the start of its first phase I trial to the end of 2020, and identified all associated trials, final development status, and FDA deliberations. We classified trials as pediatric-eligible if patients aged < 18 years were eligible for participation. We used the Drugs@FDA website to identify all FDA actions, including marketing approvals and requests for pediatric trials under pediatric programs (i.e. BPCA requests or PREA requirements). Results: A total of 572 NMEs started initial phase I clinical trials in 2010-2015. Among these, the most studied classes were small molecules (N, %: 316, 55%), antibodies (148, 26%), and antibody-drug conjugates (44, 8%). Overall, the NMEs were studied in 6,141 clinical trials by the end of 2020, with a median of 3 trials per NME. The highest pre-approval development phase reached by an NME was phase I for 325 (57%), phase II for 153 (27%), and phase III for 94 (16%). Only 39 NMEs (7%) were approved by the FDA by the end of 2020. Among approved NMEs, the median time (range) from start of first phase I trial to date of first approval was 6 (3-10) years. Among all NMEs, only 67 (12%) were tested in pediatric-eligible trials by the end of 2020, and 5 (< 1%) were approved for use in selected pediatric populations. Three of these had been subject to BPCA requests, and all had PREA requirements waived. Conclusions: More efficient clinical development strategies are needed to accelerate the production of new cancer therapies, especially for children. Analyses such as this one should be conducted regularly to help identify areas in need of innovation and to assess the potential impact of regulatory initiatives (e.g. the RACE act, effective since August 2020).