EU regulator changes its mind on Mirati's KRAS inhibitor Krazati with a thumbs-up following initial snub

Mirati Therapeutics’ KRAS inhibitor Krazati’s EU prospects weren’t looking good after an initial rejection from Europe's drugs regulator. Now, the European Medicines Agency’s (EMA's) Committee for Medicinal Products for Human Use (CHMP) has come around on the drug after taking a second look.

The CHMP first rebuffed the med back in July, finding that it didn’t meet certain requirements for a conditional marketing authorization, despite acknowledging its positive risk-benefit profile. Mirati, disagreeing, filed for a formal re-examination that ultimately resulted in the recent positive opinion.

Now, European patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) will soon have a new treatment option in Mirati’s flagship drug. The company was already supplying the therapy to eligible patients in the EU based on “individual requests” from healthcare professionals, it said in July.

This will be good news for Bristol Myers Squibb, which last month put $5.8 billion on the table to buy out Mirati for Krazati. 

"We look forward to approval from the European Commission and the opportunity to positively impact the lives of eligible patients living in the European Union,” CEO Alan Sandler, M.D., said in the company’s release.

Along with the CHMP nod, Krazati last week scored a conditional marketing authorization from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) and received its FDA accelerated approval late last year.  

KRAS was once considered an undruggable target, or as Mirati puts it “one of the most challenging mutations in cancer research.” Krazari’s approvals marked the second KRAS inhibitor on the market after Amgen’s Lumakras nabbed its green light in 2021 in what the company called a “breakthrough moment.”

With multiple options, “physicians will better be able to tailor their treatment for each patients,” Martin Reck, M.D., PhD, of Germany’s Grosshansdorf Lung Clinic pointed out in Mirati’s release, noting that each patient has a “slightly different” case.

Mirati claims a differentiated clinical profile for its Krazati, it noted after the EU’s original rejection. According to the company, such differentiators include its drug’s efficacy profile, potential central nervous system activity and combinability with other agents, including at the same time or after treatment with an immune checkpoint inhibitor.

Krazati brought Mirati $16.4 million in revenue over the third quarter. Amgen, meanwhile, pulled $52 million over the same period for its Lumakras, though it was recently hit with a setback from an FDA advisory committee.

A panel of outside experts in October questioned if the primary endpoint could be reliably interpreted in a key trial, a concern shared with the FDA. The agency pointed out “multiple sources of systemic bias” in its briefing documents, but still sees potential benefits from the drug.