FDA Approves BMS's KRAS Inhibitor for Colorectal Cancer

The FDA recently granted accelerated approval for Bristol Myers Squibb's KRAS inhibitor, Krazati (adagrasib), in combination with cetuximab. This approval targets patients with KRASG12C-mutated, locally advanced, or metastatic colorectal cancer (CRC) who have previously been treated with chemotherapy regimes including fluoropyrimidine, oxaliplatin, and irinotecan. Bristol Myers Squibb acquired Krazati through its $5.8 billion purchase of Mirati Therapeutics last year.

The approval is based on promising data from the Phase I/II KRYSTAL-1 study. In this study, Krazati demonstrated a confirmed overall response rate of 34% in 94 CRC patients. The participants also experienced a median duration of response lasting 5.8 months. This regulatory win follows a priority review process, providing a morale boost for the drug as it approaches its next big challenge—gaining full approval for treating lung cancer.

Krazati had previously received accelerated approval in 2022 for patients with KRAS-mutant, locally advanced, or metastatic non-small-cell lung cancer (NSCLC). A March readout of the Phase III KRYSTAL-12 study had initially suggested favorable outcomes for the drug in this setting. Bristol Myers Squibb reported that the drug met its primary endpoint of progression-free survival (PFS). However, subsequent detailed data released at the American Society of Clinical Oncology (ASCO) annual meeting cast some doubt on what had seemed like a clear victory. The detailed results showed that Krazati achieved a PFS of 5.49 months compared to 3.84 months for chemotherapy, a statistically significant improvement. However, this fell short of the expectations set by analysts at TD Cowen, who opined that a four-month delay in cancer progression relative to docetaxel would be necessary to deem the trial a success.

The recent approval for colorectal cancer might mitigate some uncertainties surrounding Krazati's efficacy in lung cancer. The drug has thus far navigated challenging terrains where other KRAS inhibitors have struggled, especially in lung cancer. As such, the latest FDA approval could build confidence among stakeholders, even as questions linger about its broader clinical utility.

In conclusion, Bristol Myers Squibb's Krazati (adagrasib) has gained a significant milestone by securing FDA approval for a new indication in colorectal cancer, following its earlier approval in lung cancer. The drug’s future prospects, particularly in lung cancer treatment, remain closely watched by both the medical community and market analysts.