TY - JOUR
T1 - A demand-offer critical analysis of current drug development. Phase I drugs versus TCGA sequencing data
AU - Repetto, Matteo
AU - Crimini, Edoardo
AU - Belli, Carmen
AU - Boscolo Bielo, Luca
AU - Ascione, Liliana
AU - Meric-Bernstam, Funda
AU - Drilon, Alexander
AU - Curigliano, Giuseppe
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/9
Y1 - 2023/9
N2 - Background: Phase 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. Methods: Ranging 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. Results: A 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. Conclusions: The 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.
AB - Background: Phase 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. Methods: Ranging 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. Results: A 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. Conclusions: The 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.
KW - Early drug development
KW - Precision medicine
KW - TCGA
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U2 - 10.1016/j.ejca.2023.112958
DO - 10.1016/j.ejca.2023.112958
M3 - Article
C2 - 37451181
AN - SCOPUS:85164662066
SN - 0959-8049
VL - 190
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 112958
ER -