FDA Grants Breakthrough Therapy Status to Elironrasib from Revolution Medicines

Revolution Medicines, Inc., a clinical-stage oncology company, has announced that the U.S. Food and Drug Administration (FDA) has awarded Breakthrough Therapy Designation to their drug elironrasib. This designation is for the treatment of adult patients suffering from KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have previously undergone chemotherapy and immunotherapy but have not been treated with a KRAS G12C inhibitor.

The designation comes in response to promising results from the Phase 1 RMC-6291-001 clinical trial, which evaluated the effectiveness of elironrasib as a monotherapy for patients with advanced KRAS G12C solid tumors. The trial demonstrated significant antitumor activity, favorable safety and tolerability profiles, along with an impressive objective response rate and progression-free survival.

Mark A. Goldsmith, M.D., Ph.D., CEO and chairman of Revolution Medicines, emphasized the need for new targeted treatments for RAS-addicted cancers. He highlighted that the FDA's recognition of elironrasib underscores its therapeutic potential, particularly in treating patients with KRAS G12C-mutated lung cancer. This announcement follows closely on the heels of another designation for daraxonrasib, intended for patients with advanced RAS mutant pancreatic cancer. Goldsmith noted that these advancements validate the company's innovative approach in developing potential treatments for RAS mutant cancers.

Elironrasib is engineered as a selective inhibitor that binds covalently to the oncogenic RAS(ON) form of the RAS G12C variant, which is a driver in about 12% of NSCLC cases. Revolution Medicines is actively pursuing the exploration of elironrasib both as a standalone treatment and in combination with other therapies, aiming to advance its development through various clinical trials.

Non-small cell lung cancer (NSCLC) represents a significant portion of lung cancer cases, accounting for 80-85% of all occurrences. Unfortunately, most patients are diagnosed at advanced or metastatic stages, where treatment becomes more challenging. KRAS mutations occur in nearly 30% of NSCLC cases, with KRAS G12C being the most prevalent mutation. Despite the prevalence, no RAS-targeted inhibitors have received full FDA approval for treating KRAS G12C NSCLC, highlighting an unmet medical need.

The Breakthrough Therapy Designation is part of the FDA's efforts to expedite the development and review of new medicines targeting serious conditions with significant unmet needs. This designation requires that preliminary clinical evidence demonstrates substantial improvement over existing treatments on clinically significant endpoints.

Revolution Medicines is committed to the development of novel targeted therapies for RAS-addicted cancers. Their research and development pipeline includes RAS(ON) inhibitors designed to target various oncogenic RAS protein variants. Currently, the company is advancing several RAS(ON) inhibitors through clinical development, including daraxonrasib, elironrasib, and zoldonrasib. The future pipeline is also poised to include other RAS(ON) mutant-selective inhibitors, with plans for expanding clinical trials further.

With more than 197,000 people diagnosed with NSCLC in the United States every year, the disease remains a leading cause of cancer-related deaths worldwide. This is largely due to late-stage diagnoses and the limited efficacy of traditional therapies, underscoring the urgent need for effective new treatments like elironrasib. Revolution Medicines aims to address this critical need through ongoing research and development efforts, potentially offering new hope to patients with RAS-addicted cancers.