The FDA has greenlit a Mirati Therapeutics drug for lung cancer, giving the biotech its first approved product and making the pill the second one designed to address a particularly elusive target. The regulatory decision puts the Mirati drug in direct competition with an Amgen drug that last year became the first one approved to drug this target, a mutation called KRAS.

The Mirati drug, adagrasib, is approved as a second line treatment for advanced non-small cell lung cancer (NSCLC) characterized by a subset of the KRAS mutation called KRAS G12C. San Diego-based Mirati will market its twice-daily pill as “Krazati.”

KRAS is a gene that codes for a protein involved in cell signaling. It was long thought to be “undruggable” because the proteins that stem from the mutated gene lack the typical places to which a small molecule drug can bind. Krazati is designed to bind to the mutant form of KRAS G12C protein, locking it in an inactive state and stopping it from sending the uncontrolled signals that drive cancer.

The FDA decision for Krazati is based on the results of an open-label Phase 2 study that tested the drug in 116 patients who had previously been treated with chemotherapy and a type of immunotherapy called a checkpoint inhibitor. The main goals were to measure the objective response rate, which is an assessment of the number and size of tumors, as well as the duration of response. Results showed a 43% objective response rate and a median duration of response of 12.5 months. Mirati aims to make the case that its drug is the better KRAS G12C blocker.

Krazati’s results for its trial’s two main goals are better than what Amgen’s Lumakras posted in the study leading up to its FDA approval, though it must be acknowledged that the comparison does not come from a head to head study. The most common adverse reactions reported in the Krazati study included nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, liver toxicity, all of which are similar to the adverse effects reported in the tests of Amgen’s drug.

One potentially key differentiating feature of the Mirati drug is its ability to penetrate into the brain. NSCLC often spreads to the brain, where it is very difficult to treat. A retrospective analysis of the Phase 2 results found an intracranial overall response rate of 33%. However, the company noted in an investor presentation that that response cannot be attributed to Krazati alone as the patients already had stable and adequately treated brain metastases. However, oncologists are aware of the brain-penetrating capabilities of the Mirati drug, according to Alexander Spira, co-director of the Virginia Cancer Specialists Research Institute and the lead investigator for the Krazati clinical studies.

“The [central nervous system] activity is already well described and well known and is already being talked about in the oncologic community as both a differentiating factor and an important aspect of the use of the drug,” Spira said, speaking during a Mirati conference call Tuesday.

The biotech set a $19,750 list price for a 30-day supply of Krazati, topping the $17,900 monthly cost of Amgen’s Lumakras. Speaking on a Tuesday conference call, Chief Commercial Officer Ben Hickey said the price is “a small premium to Lumakras, which we think represents the innovation that we’re bringing to market.”

Mirati aims to address a market of what it estimates is 7,000 NSCLC patients with KRAS G12C mutation who are diagnosed annually in the U.S. and fall under the second-line setting. The company aims to go beyond second-line treatment by testing it as a monotherapy and in combination with other therapies. The company is also exploring use of the drug in other solid tumors, including colorectal cancer and pancreatic cancer.

Concurrent with Krazati’s approval, the FDA also approved companion diagnostics from both Agilent Technologies and Qiagen that will identify patients whose NSCLC is characterized by the KRAS G12C mutation. The regulatory decision for Krazati, based on the Phase 2 results, was an accelerated approval based on less evidence than is required for a drug under standard review. The company is generating additional evidence from a larger clinical trial now underway that will serve as the confirmatory study. This Phase 3 study will compare Krazati to docetaxel, a type of chemotherapy. The two main goals of the study are to measure progression-free survival and overall survival. Chief Medical Officer Alan Sandler said Mirati believes that the company has the opportunity to secure full approval if the trial achieves either of those goals.

Photo by Mirati Therapeutics