On July 21, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion on the Conditional Marketing Authorisation Application (MAA) for KRAZATI (adagrasib) for treatment of patients with KRASG12C -mutated advanced non-small cell lung cancer (NSCLC) (Press release, Mirati, JUL 21, 2023, View Source [SID1234633363]) .
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Mirati disagrees with the opinion and intends to request a formal re-examination.
CHMP states that KRAZATI has a positive risk-benefit profile, however, does not fulfill certain requirements for a Conditional Marketing Authorisation. Mirati believes KRAZATI addresses the Conditional Marketing Authorisation requirements despite there being a currently conditionally approved KRASG12C inhibitor and that KRAZATI possesses a differentiated clinical profile. Key differentiators include KRAZATI’s efficacy profile, potential central nervous system activity and combinability with other agents, including concurrent with or following treatment with an immune checkpoint inhibitor.
"We remain steadfast in our belief in the potential of adagrasib to provide hope for patients in the European Union," said David Meek, chief executive officer, Mirati Therapeutics, Inc. "We will continue to work closely with the EMA and the CHMP to bring adagrasib to eligible patients. We are committed to delivering therapeutic options for patients living with KRASG12C-mutated NSCLC in the EU, as we have in the United States following the Accelerated Approval of KRAZATI in December 2022."
The MAA for KRAZATI was based on the Phase 2 registration-enabling cohort of the KRYSTAL-1 study, evaluating KRAZATI 600 mg administered orally twice daily in 116 patients with KRASG12C-mutated advanced NSCLC who previously received treatment with a platinum-based regimen and an immune checkpoint inhibitor.
Mirati is supplying KRAZATI to eligible European patients with a KRASG12C mutation based on individual requests from healthcare professionals. Mirati intends to continue supplying KRAZATI under early access in EU Member States in alignment with applicable laws and regulations.
This decision will have no impact on any of Mirati’s clinical trials. Study enrollment for KRYSTAL-12, the confirmatory Phase 3 trial evaluating adagrasib versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRASG12C mutation, is progressing as expected. Progression-free survival and interim overall survival results are anticipated in the first half of 2024.
About KRAZATI (adagrasib)
Mirati has risen to meet one of the most challenging mutations in cancer research by developing KRAZATI, a highly selective and potent oral small-molecule inhibitor of KRASG12C.
Intentionally designed to meet the challenge of KRASG12C, adagrasib is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24-48 hours.1 Adagrasib has shown clinically to be a CNS penetrant, which may be important given that CNS metastases frequently occur in NSCLC and lead to poor prognosis.2,3,4
The FDA provided KRAZATI Accelerated Approval (Subpart H), allowing for the approval of drugs that treat serious conditions, and that fill an unmet medical need based on surrogate endpoints. Adagrasib continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.
About the KRYSTAL-1 Study
KRYSTAL-1 is an open-label Phase 1/2 multiple-expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anti-cancer therapies in patients with advanced solid tumors harboring the KRASG12C mutation.
About KRASG12C in NSCLC
Lung cancer is one of the most common cancers worldwide, accounting for 2.21 million new cases and 1.8 million deaths worldwide in 2020.5 Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases.6 KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14% of patients with lung adenocarcinoma, and is a biomarker mutation of poor prognosis.