A decade of approved first-in-class small molecule orphan drugs: Achievements, challenges and perspectives

Jinying Gu; Qiuyu Wu; Qiuyue Zhang; Qidong You; Lei Wang

doi:10.1016/j.ejmech.2022.114742

A decade of approved first-in-class small molecule orphan drugs: Achievements, challenges and perspectives

Eur J Med Chem. 2022 Dec 5:243:114742. doi: 10.1016/j.ejmech.2022.114742. Epub 2022 Sep 9.

Authors

Jinying Gu¹, Qiuyu Wu¹, Qiuyue Zhang¹, Qidong You², Lei Wang³

Affiliations

¹ State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
² State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: youqd@163.com.
³ State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: leiwang.91@cpu.edu.cn.

PMID: 36155354
DOI: 10.1016/j.ejmech.2022.114742

Abstract

In the past decade (2011-2020), there was a growing interest in the discovery and development of orphan drugs for the treatment of rare diseases. However, rare diseases only account for a population of 0.65‰-1‰ which usually occur with previously unknown biological mechanisms and lack of specific therapeutics, thus to increase the demands for the first-in-class (FIC) drugs with new biological targets or mechanisms. Considering the achievements in the past 10 years, a total of 410 drugs were approved by U.S. Food and Drug Administration (FDA), which contained 151 FIC drugs and 184 orphan drugs, contributing to make up significant numbers of the approvals. Notably, more than 50% of FIC drugs are developed as orphan drugs and some of them have already been milestones in drug development. In this review, we aim to discuss the FIC small molecules for the development of orphan drugs case by case and highlight the R&D strategy with novel targets and scientific breakthroughs.

Publication types

Review

MeSH terms

Drug Approval
Drug Development
Humans
Orphan Drug Production*
Rare Diseases* / drug therapy
United States
United States Food and Drug Administration