Utilization of phase I studies for target validation of first-in-class drugs.

Autor: Kawabe Y; Research Division, Chugai Pharmaceutical Co., Ltd, 216 Totsuka-cho, Totsuka-ku, Yokohama, Kanagawa 2449602, Japan. Electronic address: kawabeysk@chugai-pharm.co.jp., Himori M; Research Division, Chugai Pharmaceutical Co., Ltd, 216 Totsuka-cho, Totsuka-ku, Yokohama, Kanagawa 2449602, Japan., Watanabe Y; Research Division, Chugai Pharmaceutical Co., Ltd, 216 Totsuka-cho, Totsuka-ku, Yokohama, Kanagawa 2449602, Japan., Davis J; Research Division, Chugai Pharmaceutical Co., Ltd, 216 Totsuka-cho, Totsuka-ku, Yokohama, Kanagawa 2449602, Japan., Hamada H; Research Division, Chugai Pharmaceutical Co., Ltd, 216 Totsuka-cho, Totsuka-ku, Yokohama, Kanagawa 2449602, Japan.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2024 Nov; Vol. 29 (11), pp. 104200. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1016/j.drudis.2024.104200
Abstrakt: This review discusses the growing importance of target validation within phase I (P1) trials as a new trend in drug development, especially in establishing proof of concept (POC) for first-in-class drugs. The paper describes two approaches: the P1-PIV approach, which directly evaluates the primary endpoint for a pivotal clinical study to confirm therapeutic effects during P1, and the newly introduced P1-FCTE, which assesses functional changes necessary for therapeutic effect as a novel target validation milestone in P1. By providing practical examples of first-in-class drugs, we compare the benefits, costs, hurdles and applicable therapeutic areas of these approaches. Finally, we discuss the potential of these novel approaches to facilitate POC success, shorten development timelines and ultimately increase drug discovery success rates.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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