On further review, KRAS inhibitors aren’t alike

It’s rare for the CHMP to reverse an approval refusal, but that’s precisely what happened on Friday, with Mirati’s Krazati being the lucky beneficiary. The outcome is relevant beyond the EU, which looks like a smaller opportunity than the drug’s niche approved use in the US, and hints again that Krazati is the better of the two approved KRAS G12C inhibitors. The CHMP had issued a negative opinion on Krazati on 21 July, saying the drug’s Krystal-1 trial didn’t meet the criteria for a conditional approval; Mirati requested formal re-examination. On Friday, in reversing its negative stance, the CHMP revealed that when rejecting Krazati it had also taken into consideration Codebreak-200, the controversial rival study of Amgen’s Lumakras. The committee now admits that Codebreak-200’s highly ambiguous results “are not necessarily relevant for Krazati”, which has a different safety profile and is sufficiently backed by Krystal-1 after all. Though this isn’t mentioned, Codebreak-200 was savaged by a US adcom last month, a fact that the CHMP will have been aware of. KRAS competition is coming, from Roche, Lilly and others, but for now it seems that Bristol Myers Squibb picked the perfect moment to acquire Mirati.