BMS, Mirati's Krazati Secures FDA Approval, Surpasses Amgen's Lumakras in Colorectal Cancer

Bristol Myers Squibb (BMS) has secured a significant advantage in the competitive KRAS inhibitor market with its cancer treatment, Krazati. Though it was introduced after Amgen's Lumakras, Krazati has gained a lead thanks to recent developments and FDA approvals.

On a notable Friday, the U.S. FDA granted accelerated approval for Krazati, in combination with Eli Lilly’s Erbitux (cetuximab), to treat certain chemotherapy-experienced adults with KRAS-mutated locally advanced or metastatic colorectal cancer (CRC). This approval is conditional, requiring BMS to validate Krazati's benefits in CRC through a confirmatory trial to maintain its market authorization.

This approval follows Krazati’s initial authorization in December 2022 for previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC). Krazati, also known as adagrasib, became the second KRAS-targeting drug in the U.S. market, following Lumakras’ debut for NSCLC in May 2021.

BMS acquired Krazati through its purchase of Mirati Therapeutics for approximately $4.8 billion, finalizing the transaction in January. Krazati's approval marks a significant milestone, as KRAS G12C mutations occur in about 3% to 4% of CRC patients and have been notoriously challenging to treat. Dr. Rona Yaeger, a gastrointestinal oncologist at Memorial Sloan Kettering Cancer Center, highlighted the historical difficulties in managing this condition.

The FDA’s decision was based on promising early outcomes from the KRYSTAL-1 phase 1/2 trial, involving 94 patients. In this open-label study, participants received 600mg tablets of Krazati twice daily alongside Erbitux administered weekly or biweekly. The treatment achieved a confirmed objective response rate (ORR) of 34%, the primary endpoint, and a median duration of response (DOR) of 5.8 months. Notably, 31% of patients who responded to Krazati experienced a DOR of at least six months.

The current late-line standard treatments for CRC show limited effectiveness, with ORRs ranging between 1% and 6% after chemotherapy progression, underscoring Krazati's potential as a more effective alternative.

In addition to expanding its indications beyond Lumakras', Krazati solidified its leadership in the KRAS inhibitor race with positive results from the late-stage KRYSTAL-12 study in March. The study revealed that Krazati significantly reduced the risk of tumor progression or death compared to chemotherapy in certain NSCLC patients.

This success represents a setback for Lumakras, especially after Amgen's recent efforts to obtain full approval for its KRAS inhibitor faced challenges. The FDA and external advisers found the progression-free survival data from the phase 3 CodeBreaK 200 trial unreliable. Nonetheless, Lumakras remains on the market while Amgen conducts another confirmatory study, expected to complete by February 2028.

Amgen is also seeking approval for Lumakras in CRC. The company reported that its phase 3 CodeBreaK 300 trial showed Lumakras, combined with Vectibix, extended median progression-free survival to 5.6 months compared to 2.2 months for standard treatments in chemo-refractory KRAS G12C colorectal cancer.

During its first earnings quarter under BMS, Krazati generated $21 million in revenue over the first three months of 2024, indicating strong market performance and interest in this promising cancer treatment.