FDA Postpones Decision on Amgen's Lumakras for Colorectal Cancer

The decision date for Amgen's KRAS inhibitor, Lumakras, to be approved for metastatic colorectal cancer has been extended by the FDA to January 17, 2025. This delay, according to the company, is to allow additional time for the agency to review new supplemental data recently submitted. Originally, the FDA was expected to decide by Thursday on whether to approve Lumakras in combination with Amgen's EGFR drug, Vectibix, for patients with chemorefractory metastatic colorectal cancer possessing a KRAS G12C mutation.

Currently, Lumakras is authorized under the accelerated approval pathway for non-small cell lung cancer. Another similar KRAS inhibitor, Krazati from Bristol Myers Squibb, is approved for use in both lung cancer and colorectal cancer under the same accelerated pathway. Despite the potential, the colorectal cancer market is large, with KRAS G12C mutations responsible for only about 3% to 4% of metastatic cases. The National Cancer Institute projects that cancers of the colon and rectum will account for 8% of all new cancer diagnoses in 2024, following breast, prostate, and lung cancers in prevalence.

In June, the FDA approved Bristol Myers’ Krazati for use with Eli Lilly’s Erbitux for patients with previously treated locally advanced or metastatic colorectal cancer. Amgen's application for Lumakras approval in metastatic colorectal cancer was based on results from the CodeBreaK 300 study. The study showed a response rate of 30.2% with a 960 mg dose of Lumakras, although it did not show an improvement in overall survival. The company noted that the study wasn't designed to show a statistically significant survival benefit.

Lumakras, which became the first KRAS inhibitor to gain regulatory approval in 2021, represented a significant medical milestone. Researchers have known that KRAS mutations drive cancer, but targeting them effectively had been a longstanding challenge. However, the efficacy of KRAS inhibitors like Lumakras and Krazati has been somewhat modest.

In the realm of lung cancer, the FDA declined to convert Lumakras' accelerated approval to full approval in December, citing concerns about the pivotal trial data's reliability and noting that the median progression-free survival benefit might be significantly less than claimed by Amgen, potentially as minimal as five days.

Commercially, Lumakras has seen modest sales, with $167 million generated in the first half of the year. Meanwhile, Roche is developing its own KRAS inhibitor, divarasib, which is currently being studied in a Phase 3 trial against Krazati and Lumakras for second-line lung cancer, and in a Phase 1/1b trial for colorectal cancer. Other companies, like Revolution Medicines, are also working on developing RAS inhibitors with the hope of achieving greater effectiveness and targeting beyond the single G12C mutation to treat a broader range of patients.