The U.S. Food and Drug Administration (FDA) recently announced that sotorasib, Amgen’s investigational KRASG12C inhibitor, has been granted Breakthrough Therapy designation for locally advanced or metastatic non-small cell lung cancer (NSCLC) with KRAS G12C mutation.
The agency also accepted sotorasib into its Real-Time Oncology Review pilot program. Breakthrough Therapy designation is designed to expedite the development and review of drugs, and the Real-Time Oncology Review pilot program aims to explore a more efficient review process of marketing applications.
This isn’t the first time that investigational sotorasib, formerly AMG 510, has moved at an accelerated pace. In recent years, Amgen made changes to its R&D strategy with the goal of reducing the amount of time it takes to move the company’s most encouraging molecules from the initial discovery phase to clinical trials and through regulatory review. Sotorasib became an early example of a potentially faster approach to development. This strategy has reportedly helped the company cut an average of three years off of development timelines in the U.S.1
KRAS is one of the most commonly mutated oncogenes, and finding a target for KRAS mutations has been one of cancer research’s toughest challenges of the past 40 years.2,3 Amgen’s key discovery was a surface groove on KRAS G12C that was exploited to advance the first KRASG12C inhibitor into the clinic.
On average, a medicine takes at least ten years to go from initial discovery to being approved for patients in the U.S., according to a report from the Pharmaceutical Research and Manufacturers of America (PhRMA).4 Under Amgen’s redesigned approach, the initial decision to advance the molecule that would become sotorasib was made in Nov. 2017, and by Aug. 2018, Phase 1/2 clinical studies had begun.1,5 The FDA granted Breakthrough Therapy designation for investigational sotorasib on Dec. 7, 2020, just a little over three years after the molecule’s journey began.
- Wall Street Journal, Amgen Tasks Its Labs With Finding New Blockbuster: https://www.wsj.com/articles/amgen-tasks-its-labs-with-finding-new-blockbusters-11577638800
- Cox AD, et al. Nat Rev Drug Discov. 2014;13:828-851
- Fernandez-Medarde A, et al. Genes Cancer. 2011;2:344-358.
- PhRMA, Biopharmaceutical Research & Development: The Process Behind New Medicines: http://phrma-docs.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf
- A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreak 100): https://www.clinicaltrials.gov/ct2/show/NCT03600883