Chirality of New Drug Approvals (2013–2022): Trends and Perspectives

Abstract

Many drugs are chiral with their chirality determining their biological interactions, safety, and efficacy. Since the 1980s, there has been a regulatory preference to bring single enantiomer to market. This perspective discusses trends related to chirality that have developed in the past decade (2013−2022) of new drug approvals. The EMA has not approved a racemate since 2016, while the average for the FDA is one per year from 2013 to 2022. These 10 include drugs which have been previously marketed elsewhere for several decades, analogues of pre-existing drugs, or drugs where the undefined stereocenter does not play a role in therapeutic activity. Two chiral switches were identified which were both combined with drug repurposing. This combination strategy has the potential to produce therapeutically valuable drugs in a faster time frame. Two class III atropisomers displaying axial chirality were approved between 2013 and 2022, one as a racemate and one as a single enantiomer. ■ SIGNIFICANCE• An awareness and understanding of recent trends in new drug approvals has the potential to inform and promote innovation in new drug discovery. • Making the correct choices regarding drug chirality early in the development process can lead to a substantial cost saving given the cost of the drug approval. • Determining the impact on patients of practices such as chiral switching and drug repurposing requires data on how often such practices are leveraged.

An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023)

“…The vast majority (90%) of pyridine drugs contain a substituent in the 2-position, with disubstituted pyridines being most common (55%), of which the 2,5-substitution is most frequent. Interestingly, more than 50% of these pyridine drugs are achiral . These new pyridine-containing drugs are structurally diverse and are approved for treatment of a wide range of diseases and conditions.…”