A demand-offer critical analysis of current drug development. Phase I drugs versus TCGA sequencing data

Abstract

BackgroundPhase I clinical trials have become increasingly critical to regulatory approvals of novel agents. In phase I drug development, a global problem of unknown magnitude is the multiplicity of similar drugs being investigated against the same target, colloquially known as the ‘me too’ phenomenon. MethodsRanging from December 2020 to December 2022 we annotated phase I clinical trials present on clinicaltrials.gov.Public databases were queried for annotation of investigational agents (IAs). Extensive literature research and data mining were performed to annotate agents not present in public databases.The Cancer Genome Atlas (TCGA) pan-cancer sequencing cohort was used to perform second-level analyses to evaluate tumour types with a higher number of IA matches. ResultsA total of 1054 unique drug targets were identified. The most frequent IA classes were: cell products (1223), small-molecule inhibitors (1110), antibodies (733), and vaccines (346). Only a minority (8.9%) of phase I IAs were explored against a target without a competitive agent; 7% of agents shared targets with 2–3 other agents. Unfortunately, the majority (84%) shared targets with at least four other agents. Using data from the TCGA pan-cancer sequencing potentially underserved histologies were identified.Analysis of alteration-IA matches revealed potentially frequent and unexplored alterations in many tumour types. ConclusionsThe majority of IAs (86%) shared targets with at least three other agents. We argue that these duplicative efforts could be redirected toward unmet needs instead.