2021 First-in-Class Small Molecule Drugs

This article reviews the novel drugs approved by the FDA in February 2022. together with Dr. Naveed Yasin, Dr. Vinicius Texeira, and Dr. Jennifer Huen Three novel molecules were approved in February 2022: Small molecules: Pyrukynd (mitapivat) : An oral pyruvate kinase activator approved for the treatment of hemolytic anemia in adults with [...]

Several multi-million dollar acquisitions or license agreements took place in November 2023 for hot drug targets, with assets from selective PARP1 inhibitors to GLP1R agonists, and others. This recent news roundup highlights the notable acquisitions by pharma companies for rights to molecules in a range of different indications, with illustrative patent examples for undisclosed structures.

While gadolinium-based MRI contrast agents (GBCAs) are important for enhancing MRI and MRA imaging, several studies have shown that gadolinium can be retained in the brain and body for months to years after GBCA injection, prompting the FDA to issue box warnings to the drug class. Gadopiclenol, the ninth approved GBCA, was designed to enable use of a lower gadolinium dose than other agents. This highlight reviews how it works and why it’s notable.

Leniolisib is a selective PI3Kδ inhibitor that received approval in March 2023 from the FDA as a first-in-class treatment for activated PI3K-δ syndrome (APDS), a genetic immunodeficiency disorder caused by PI3Kδ activation. The leniolisib discovery program is notable for several reasons: it is a first approval for a PI3K inhibitor outside of oncology; the first approved drug for APDS; has a novel chemotype that appears to avoid safety issues that led to black box warnings seen with other PI3K molecules; and it overcame a polymorph issue with an early lead that led to inconsistent exposures.

Recently, we summarized the novel small molecule drug approvals of 2023 (34/55). The remaining 21 molecular entities approved were large molecules like proteins and oligonucleotides, accounting for nearly 38% of the total approvals. Notably, seven of these large molecules have earned the prestigious Breakthrough Therapy designation, relative to the two small molecules that share this recognition. A summary of approvals for large molecule drugs, accompanied by links to FDA labels and additional information pertaining to the drug's discovery and originators, appears here.