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CHMP Reverses Prior Opinion, Recommends Approval for Mirati's Krazati in KRAS-Mutant NSCLC

NEW YORK – The European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP) on Friday recommended Mirati Therapeutics' Krazati (adagrasib) for patients with KRAS G12C -mutated advanced non-small cell lung cancer who progressed after at least one prior systemic therapy.

The positive opinion comes after the CHMP re-examined its previous opinion from July, where it did not recommend approval for Krazati. CHMP initially recommended against approval because it said there were uncertainties about whether Krazati would lead to longer survival and because the drug did not meet criteria for conditional marketing authorization with another approved KRAS inhibitor in Europe. Amgen's Lumakras (sotorasib) was approved in Europe for KRAS G12C-mutant NSCLC in January 2022.

In a document explaining the re-examined opinion, CHMP noted that it initially compared the KRYSTAL-1 clinical trial results submitted for Krazati against results from the CodeBreaK 200 trial of Amgen's competing KRAS G12C inhibitor Lumakras.

"On further consideration, the Committee noted that although sotorasib and adagrasib work in a similar way, there are differences between the two medicines," CHMP wrote in the document. "Therefore, the results of the CodeBreaK 200 study are not necessarily relevant for Krazati."

CHMP also noted that the KRYSTAL-1 results showed Krazati benefits for KRAS G12C-mutant NSCLC, despite it being a small, single-arm trial. The KRYSTAL-1 results included data from 116 patients and demonstrated an overall response rate of 43 percent and 80 percent disease control rate. Median duration of response was 8.5 months.

The committee also noted that Krazati has a different safety profile and delivery method from the standard-of-care docetaxel.

"Although comprehensive data for Krazati are not yet available, the existing data were considered sufficient to justify granting a conditional marketing authorization while further data were still awaited," CHMP wrote.

Mirati will need to provide further data to the EMA from its ongoing Phase III KRYSTAL-12 study evaluating Krazati against docetaxel in previously treated KRAS G12C-mutant NSCLC.

Last week, the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) conditionally approved Krazati for advanced KRAS G12C-mutant NSCLC patients who have already received chemotherapy or anti-PD-1 immune checkpoint inhibitors. The US Food and Drug Administration granted accelerated approval to Krazati in this indication based on the KRYSTAL-1 data in December 2022.