Revolution Medicines’ RAS(ON) inhibitor daraxonrasib enters EMA phased review for pancreatic cancer, following pivotal Phase 3 survival benefit and nearing FDA rolling NDA completion.
Written By: Dr. Preethi Putti, PharmD
Reviewed By: Pharmacally Editorial Team
Revolution Medicines has entered a new regulatory stage for its investigational oral RAS(ON) inhibitor daraxonrasib, with the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) beginning a phased review of the therapy for pancreatic cancer. The process allows regulators to assess clinical, nonclinical, and manufacturing data in stages before a complete marketing authorization application is submitted, potentially shortening the overall review timeline.
The regulatory milestone follows positive findings from the pivotal Phase 3 RASolute 302 trial (NCT06625320) and comes as the company’s rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) nears completion under the FDA Commissioner’s National Priority Voucher pilot program.
Daraxonrasib has also received EMA orphan medicinal product designation for pancreatic cancer and has been selected under the agency’s Cancer Medicines Pathfinder initiative, reflecting its potential to address a significant unmet medical need in one of the deadliest solid tumors.
Phase 3 Trial Demonstrated Survival Benefit Over Chemotherapy
The global Phase 3 RASolute 302 trial evaluated daraxonrasib in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC), regardless of whether a RAS mutation had been identified.
According to the company, the study demonstrated improvements in both overall survival (OS) and progression-free survival (PFS) compared with standard cytotoxic chemotherapy. Daraxonrasib also showed a manageable safety profile while delaying deterioration in cancer-related pain, overall health status, and quality of life relative to chemotherapy.
These efficacy and patient-reported outcome data form the foundation of the ongoing regulatory submissions in the United States and Europe.
Multi-Selective RAS(ON) Inhibitor Targets Multiple RAS-Driven Tumors
Daraxonrasib is an investigational, oral RAS(ON) multi-selective, non-covalent tri-complex inhibitor that suppresses RAS signaling by blocking interactions between both wild-type and mutant RAS proteins and their downstream effectors.
The therapy is being developed for several RAS-driven cancers, including pancreatic cancer, non-small cell lung cancer (NSCLC), and colorectal cancer. Its global Phase 3 registrational program includes four studies, comprising the completed RASolute 302 trial and three additional ongoing registrational trials in PDAC and metastatic RAS-mutant NSCLC.
The FDA has previously granted daraxonrasib Breakthrough Therapy Designation and Orphan Drug Designation for previously treated metastatic PDAC harboring G12 mutations. The therapy was also selected for the agency’s National Priority Voucher pilot program, which supports accelerated development and review of treatments addressing major public health priorities.
Regulatory Momentum Builds Across Multiple Regions
Chief Executive Officer Mark A. Goldsmith, MD, PhD, said the EMA’s decision to begin a phased review reflects continued engagement with global regulatory agencies as the company moves toward potential approvals. He added that the rolling FDA submission is approaching completion and that additional regulatory filings are planned in other territories.
Pancreatic ductal adenocarcinoma remains one of the most aggressive malignancies, with approximately 80% of patients diagnosed at advanced or metastatic stages and more than 90% of tumors carrying RAS mutations. Despite available chemotherapy regimens, metastatic disease continues to have a five-year survival rate of only about 3%, highlighting the need for more effective treatment options.
If regulatory reviews progress as expected, daraxonrasib could become one of the first broad RAS-targeted therapies to offer a survival benefit in previously treated metastatic PDAC, potentially expanding treatment options for a patient population with limited therapeutic choices.
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About the Writer
Dr.Preethi Putti, PharmD (LinkedIn) is a pharmaceutical researcher with experience in healthcare and pharmaceutical market research and competitive intelligence. She specializes in analyzing drug pipelines, clinical data, and industry trends and translating complex scientific data into clear and structured medical content. Strong foundation in clinical research, data interpretation, and evidence-based healthcare analysis. Committed to advancing a global career in clinical research and healthcare innovation.