Company: Mirati Therapeutics
Used for: KRAS G12C mutation-positive cancers
Est. 2026 sales: $1.74 billion
KRAS, once thought an undruggable cancer target, could soon have its first FDA-approved medicine.
Amgen’s much-hyped sotorasib (AMG 510) looks on track to be the first to cross the finish line, as the Big Biotech filed its candidate in mid-December for previously treated non-small cell lung cancer harboring the KRAS G12C mutation. But Mirati Therapeutics’ adagrasib is following closely behind, and EvaluatePharma analysts see it as a better option than the Amgen therapy, at least for now.
Sotorasib’s FDA filing is based on phase 2 data. According to updated results from the CodeBreak 100 trial, presented at the recent World Conference on Lung Cancer, sotorasib triggered response in 37% of patients with KRAS G12C-mutated NSCLC. The response lasted a median 10 months.
The 37% overall response rate was a slight improvement from the 35% Amgen reported last fall for the phase 1 portion of the trial, but it was still below the 45% Mirati’s adagrasib (MRTX849) triggered in its own ongoing phase 1/2 Krystal-1 trial.
Adagrasib’s tumor reduction potential appears to be much deeper, SVB Leerink analysts noted to investors in October. About 70% of adagrasib responders had tumor responses greater than 40% from baseline, while only 47% of phase 1 study patients on sotorasib could say the same.
Cross-trial comparisons should be made with caution, given different trial designs and patient profiles. At this point, the competition appears to tip in Mirati’s favor, but the fight isn’t conclusive yet.
For one thing, adagrasib elimited tumors completely in just one study patient, while sotorasib did it in three. But the trials were simply too small to read anything meaningful into these numbers.
Adagrasib’s stronger efficacy was also weighed down by side effects. In February, SVB Leerink analyst Geoffrey Porges noted a safety advantage for sotorasib, pointing to increased incidence of the heart rhythm problem QT prolongation in adagrasib’s study.
Mirati still hasn’t reported its registrational phase 2 data, and a phase 3 confirmatory trial against docetaxel in second-line NSCLC is being planned to start this quarter. Tumor shrinkage data only offer an early peek at efficacy; the all-important overall survival data, which show whether a drug can lengthen patients' lives, are not available for either candidate.
Mirati has projected a new drug application in the second half of 2021, potentially giving Amgen a few months' head start on the market.
But monotherapy is just the entry point; combination trials could open up more possibilities, the SVB Leerink team noted. Mirati could report phase 1/1b adagrasib combination data with Merck & Co.’s PD-1 blocker Keytruda in first-line NSCLC and with Eli Lilly’s EGFR inhibitor Erbitux in second-line colorectal cancer later this year.
As of January, EvaluatePharma projected 2026 adagrasib sales of $1.74 billion, versus $1.51 billion for sotorasib for Amgen and its Chinese partner BeiGene by that time.