An Amgen drug that won fast-track FDA approval last year for some types of lung cancer already has preliminary data from a larger study showing the pills beat standard chemotherapy. These results are enough to meet the primary goal of the clinical trial, but you’ll have to wait to see more information. Amgen retains detailed data for presentation at an unspecified future medical appointment.
Thousand Oaks, California-based Amgen announced preliminary results for its drug Lumakras after the market closed on Tuesday. While the results provide further validation of the drug, the question now is whether they are also enough to turn the FDA’s accelerated approval into full. If so, that could put adagrasib, a competing drug from Mirati Therapeutics, in a tough spot.
Both Lumakras and adagrasib are small molecules designed to target mutations of KRAS, a gene that plays a role in cell signaling. KRAS mutations can cause uncontrolled cell growth. Their role in promoting cancer is understood, but these mutations are difficult targets for drugs. Amgen and Mirati’s small molecules are designed to address a subset of KRAS mutations called KRAS G12C.
The FDA’s accelerated approval of Lumakras last year made it the first approved drug targeting any KRAS mutation. This regulatory decision is based on results from an open-label phase 2 study that tested the therapy in 124 patients with non-small cell lung cancer (NSCLC) characterized by the KRAS G12C mutation. The approval covers the drug’s use as a second-line treatment for this type of cancer.
The results, announced by Amgen on Tuesday, came from a phase 3 study involving 345 patients whose NSCLC with the KRAS G12C mutation had been treated with at least one prior systemic therapy. Study participants were randomly assigned to receive either Lumakras or docetaxel, a standard chemotherapy. Amgen said preliminary results showed the drug met the primary goal of progression-free survival, a measure of how long patients live without their cancer getting worse. Although the pharmaceutical giant said its drug demonstrated statistical significance and superiority on this endpoint, it did not elaborate on those results.
“Further analyzes of the data are ongoing and we look forward to sharing detailed data at an upcoming medical meeting,” said David Reese, Amgen’s executive vice president of research and development, in a prepared statement.
The accelerated approval program allows earlier approval of drugs based on less data than is required in a standard review. This pathway is reserved for drugs that treat serious conditions with few or no therapeutic options. Drugs granted accelerated approval must undergo additional clinical testing to confirm their benefit. Amgen’s Phase 3 trial of Lumakras may fulfill this requirement.
Mirati has too submitted for expedited approval of its KRAS G12C-blocking drug based on data from a phase 1/2 study. The FDA has set a December 14 target date for a regulatory decision. The potential problem for the San Diego-based biotech is timing. If Amgen’s drug wins full FDA approval before Mirati’s adagrasib decision, it could undermine Mirati’s case for accelerated approval. That’s because having a drug with full approval means that other drugs that follow it may have to meet the same evidentiary standard to pass FDA review. Adagrasib is not necessarily eliminated from competition. But a decision on this drug may have to wait until it gets its own supporting data from a well-controlled phase 3 study. That phase 3 study is still ongoing.
Mirati reported phase 2 data for adagrasib in June at the American Society of Clinical Oncology (ASCO) annual meeting. These results show efficacy comparable to the phase 2 data that support the approval of Lumakras. Mirati said it hopes to differentiate its drug by offering a better ability to treat NSCLC that has metastasized to the central nervous system. Mirati’s ASCO presentations are also included encouraging results by this measure, albeit in a small number of patients. How the FDA weighs these results could also affect the accelerated approval decision for adagrasib.
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