Efficacy End Points and Dose Analysis of Food and Drug Administration-Approved Novel Drugs in 2020.

ABSTRACT

Background: During 2020, the Food and Drug Administration approved 53 novel drugs. Objective: Biomarkers, surrogate endpoints and dosing regimens used in early and pivotal clinical stages are evaluated. Methods: Information on various efficacy end points of 2020 Food and Drug Administration approved novel drugs was gathered from the Drug Approvals and Databases page of the Food and Drug Administration website. Endpoint data from efficacy end points for the 2019 approved novel drugs by Tong and Wang are used as a comparison. Results: Among the 53 drugs approved during 2020, 49 were for treatment of various diseases and 4 were for diagnostics. Twenty-five drug approvals (51%, relative to 49 drugs for treatment of diseases) were based on surrogate end points, consisting of 12 accelerated approvals and 13 regular approvals. There were 19 drug approvals for cancer treatments (39%, relative to 49 drugs for treatment of diseases). During 2019, there were 48 drugs approved. Forty-four were for treatment of various diseases and 4 were for diagnostics. Fourteen drug approvals (32%, relative to 44 drugs for treatment of diseases) were based on surrogate end points, consisting of 9 accelerated approvals and 5 regular approvals. There were 10 drug approvals for cancer treatments (23%, relative to 44 drugs for treatment of diseases).The approved doses were usually much closer to the highest dose tested in clinical trials (about 2-fold lower) compared with the lower dose tested in clinical trials (about 11-fold higher). Large and variable distances between the starting low dose in humans and the final approved doses indicate that finding the optimal dose in clinical trials is still a time-consuming and costly process. Further dose analysis for cancer drugs approved during 2020 showed that the distances between the starting dose in human beings and the final approved doses of cancer drugs were still large and variable, similar to distances in noncancer drugs. Stratification of drugs approved in 2020 by molecular weights shows that small molecular weights (<1000 Daltons) appeared to be smaller and less variable than those for drugs with large molecules (>1000 Daltons). (Curr Ther Res Clin Exp. 2022; 83XXX-XXX). Conclusions: Surrogate end points with accelerated approval have been widely used for approvals, with an increasing trend from 2019 to 2020 (32% vs. 51%). The approved doses usually were much higher (10-fold) than the lowest tested dose in first-in-human trials, while much closer (2-fold lower) to the highest dose tested in clinical trials.