On Dec. 12, 2022, the U.S. Food and Drug Administration (FDA) granted Accelerated Approval to Krazati™ (adagrasib – Mirati Therapeutics) tablets. It is indicated as second-line or later therapy for adult patients who have advanced or metastatic non-small cell lung cancer (NSCLC) that tests positive for mutations in KRAS G12C, a protein involved in the growth of cells. The recommended dose of Krazati is 600mg (three tablets) twice a day. At a wholesale acquisition cost (WAC) of $19,750 per 30-day supply (180 tablets), it will be dispensed through a small network of specialty pharmacies that does not include Accredo. A launch date has not yet been announced. For its complete prescribing information, look here.
At a Glance
- Brand (Generic) Name: Krazati (adagrasib)
- Manufacturer: Mirati Therapeutics
- Date Approved: Dec. 12, 2022
- Indication: to treat adults who have KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, and who have received at least one prior systemic therapy
- Dosage Forms Available: 200mg tablets
- Launch Date: The launch date isn’t known at this time.
- Estimated Annual Cost: approximately $237,000 (WAC)
- According to the American Cancer Society (ACS), lung cancer is the second most common cancer type among Americans with about 240,000 cases diagnosed annually. NSCLC accounts for up to 85% of all lung cancer cases.
- Mutations in KRAS, a protein that contributes to cell growth, cause too much of its production, which increases cancer growth. They are estimated to be present in about 13% of patients who have NSCLC.
- By attaching to KRAS G12C, Krazati keeps it from promoting the growth of cancer cells.
- In the open-label, phase II KRYSTAL-1 clinical study, which included 112 patients, the overall response rate (ORR) to Krazati was 43% and responses lasted an average of 8.5 months.
- In the trial, one-quarter or more of patients experienced side effects that included decreased appetite, diarrhea, difficulty breathing, fatigue, kidney damage, liver damage, muscle and bone pain, nausea, swelling, and vomiting. Much smaller percentages of participants had serious abnormalities in blood components, electrolytes, and/or liver enzymes.
- Although multiple other drugs are FDA approved to treat NSCLC, the only other KRAS G12C inhibitor available in the U.S. is Amgen’s Lumakras® (sotorasib) tablets, which received Accelerated Approval from the FDA in May 2021 for KRAS G12C-positive NSCLC.
- Because Accelerated Approval for Krazati was based on the results of phase II clinical study, additional positive results from more advanced trials will be needed before full FDA approval is granted. It was approved under the FDA’s Breakthrough Therapy and Real-Time Oncology Review (RTOR) processes.
- Alone and in combination with other drugs, Krazati is in various stages of clinical trials for treating colorectal cancer (CRC), pancreatic cancer, and other advanced solid cancers that have KRAS mutations.