Bristol Myers Squibb won accelerated approval on Friday to take its KRAS inhibitor to colorectal cancer patients.
Krazati will now be available for use with Eli Lilly’s Erbitux (cetuximab) for certain locally advanced or metastatic patients who have been previously treated and have a KRAS G12C mutation. Those patients typically have poor outcomes and few options, according to Bristol Myers, which snagged the drug in its $4.8 billion Mirati buyout.
KRAS, once considered an “undruggable” target in cancer, acts like a switch regulating how cells grow and divide. Mutations can cause the protein to get stuck in the “on” position, leading to uncontrolled tumor cell growth. Krazati and Amgen’s rival Lumakras both work by locking the protein in “off” mode.
While many colorectal cancer patients have KRAS mutations, G12C mutations account for just 3% to 4% of patients, BMS said.
Nick Botwood“KRAS mutations are one of the most common cancer-causing mutations, and for over 40 years have been difficult to target. Colorectal tumors bearing KRAS mutations are associated with advanced disease and poor prognosis, and treatment options for these patients have been limited historically, as these mutations have been difficult to target,” Bristol Myers’ SVP of medical oncology Nick Botwood told Endpoints News ahead of the decision.
Krazati was granted an accelerated approval in certain non-small cell lung cancer patients in 2022. Bristol Myers completed its Mirati acquisition in January, then announced the following month that it had submitted new data to regulators to expand into colorectal cancer.
Krazati generated $21 million in first-quarter sales for Bristol Myers. It’s now the first KRAS drug approved for colorectal cancer, one of the most common cancers in the world. In October, Jefferies analysts predicted $1.4 billion in peak sales for Krazati in non-small cell lung cancer by 2032, and $420 million for G12C-mutated colorectal cancer.
But it could soon have more competition as well. Amgen read out positive results in colorectal cancer in combination with its Vectibix in October, and plans on filing for FDA approval in the first half of 2024.
In a Phase 1/2 trial of heavily pretreated patients, those who took Krazati and cetuximab went a median 6.9 months without worsening disease or death, and median overall survival was 15.9 months, Bristol Myers announced in April.
While it’s nearly impossible to compare data across trials, Amgen announced in October at ESMO that its 960 mg dose of Lumakras plus Vectibix led to a median progression-free survival of 5.6 months at a median follow-up of 7.8 months.
Editor’s Note: This story has been updated with additional information from Bristol Myers Squibb and the FDA’s announcement.