Gamma-secretase is most well-known as a target for Alzheimer’s disease, though such programs have not been successful to date. Nirogacestat is a gamma-secretase inhibitor that Pfizer originally intended to treat Alzheimer’s disease, but found new life at Springworks Therapeutics as a treatment as a first-in-class drug for rare and aggressive desmoid tumors (DTs). Nirogacestat received the first FDA approval for a treatment for desmoid tumors in Nov. 2023, and this article reviews how it was discovered, how the therapeutic hypothesis emerged after confusing assay disconnects, and lessons learned from the program.
8 minute read
Mar. 24, 2024
Nirogacestat (OGSIVEO): A Discarded Alzheimer’s Candidate Becomes First Approved γ-Secretase Inhibitor
nirogacestat
oral, peripherally-restricted gamma secretase inhibitor FDA approved in 2023 for desmoid tumors opt. of previously reported GSIs from cell-based screen First featured on Mar. 24, 2023 Pfizer, Groton / SpringWorks Therapeutics