Adagrasib

Revolution Medicines’ Rasonque (daraxonrasib), a potentially significant drug for pancreatic cancer has been approved by the US Food and Drug Administration. Image Credit: [Migma__Agency]/Shutterstock.com A potentially paradigm-shifting treatment for pancreatic cancer by Revolution Medicines’ (RevMed) named Rasonque (daraxonrasib) has been approved by the US Food and Drug Administration. Rasonque was the headline story at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, with strong clinical results that showed the drug could almost double overall survival (OS) compared to standard chemotherapy in previously treated pancreatic cancer patients. This was a significantly positive response in a disease where few effective drugs capable of extending survival in a meaningful way have been approved in the last few years. RevMed’s NDA for the drug was accepted a little over a month ago, and granted approval 6.5 months before the FDA’s goal date. The application was reviewed under the Commissioners National Priority Voucher Scheme that was designed to award speedy decisions. Additionally, the review was also conducted under the Real-Time Oncology Review pilot that allows rolling submissions. The drug already had a Breakthrough Therapy and Orphan Drug designations, and has been available through an expanded access program since May. Rasonque is an oral inhibitor of RAS, a key pathway implicated in pancreatic and lung cancer. While inhibitors like Krazati (adagrasib), which was developed by the now BMS-owned Mirati Therapeutics, and Amgen’s Lumakras (sotorasib) bind to RAS in its “off-state”, Rasonque binds the target when it’s in its “on” state . Also, both Krazati and Lumakras are limited to cancers with KRAS G12C mutations, while Rasonque is indicated for all patients with pancreatic cancer who have received at least one line of systemic therapy. RevMed’s stock has risen by more than 170% since the start of 2026, when separate rumours of an acquisition by AbbVie and MSD raised interest in the company. However, those talks did not come to fruition . The company’s market cap is now approximately $45.27bn. Prior to the approval, Rasonque sales were expected to reach $4.3bn in 2032, as per estimates by GlobalData, the parent company of Pharmaceutical Technology . In the Phase III Resolute-302 study (NCT06625320), which compared Rasonque to chemotherapy in previously treated pancreatic cancer patients, median OS was 13.2 months with the drug and 6.7 months with standard treatment. The objective response rate (ORR) was 30% on the Rasonque arm compared to 11% with chemotherapy. Rasonque is a once-daily tablet taken at a 300mg dose. In the Resolute-302 study, 44% of patients experienced Grade >3 adverse events (AE), which means the drug’s safety profile will likely need management, as per GlobalData. However, less than 2% of patients discontinued the study due to AEs. The most common side effects with the drug were rash and stomatitis. More recently, the company released positive results with its next RAS inhibitor— the G12D RAS-mutation-targeting zoldonrasib —in combination with chemotherapy as a first-line treatment for RAS G12D-mutated pancreatic cancer. In the interim analysis, 82% of patients treated with the combination had an objective response, and 61% with zoldonrasib alone.

The US FDA has approved Rasonque (daraxonrasib), Revolution Medicines' first-in-class RAS(ON) multi-selective inhibitor, for adults with metastatic pancreatic adenocarcinoma following prior systemic therapy or who are not candidates for multiagent systemic therapy. The biomarker-unrestricted approval gives Revolution Medicines its first commercial product and brings RAS-directed therapy to a broad pancreatic cancer population, where oncogenic RAS alterations are present in approximately 90–95% of tumors. The FDA granted the approval 6.5 months ahead of the product's user fee deadline under the Commissioner's National Priority Voucher pilot program. Rasonque had also received Breakthrough Therapy, Orphan Drug, and Priority Review designations. The drug is administered orally once daily, and the approved indication does not require testing for a specific RAS mutation. Approval was supported by the randomized, open-label Phase III RASolute 302 trial, which enrolled 500 adults with previously treated metastatic PDAC. Daraxonrasib nearly doubled median overall survival to 13.2 months from 6.7 months with investigator's choice of standard chemotherapy, corresponding to a 60% reduction in the risk of death reported at ASCO 2026. The most common adverse events included rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. Daraxonrasib is designed to inhibit multiple oncogenic RAS variants by recruiting cyclophilin A to form a tri-complex with RAS, blocking downstream signaling. Its activity spans common PDAC-associated mutations including KRAS G12D, G12V, and G12R, distinguishing it from earlier mutation-specific KRAS inhibitors such as sotorasib and adagrasib, which target KRAS G12C — a variant found in only approximately 1–2% of pancreatic cancers. The approval represents a major validation of Revolution Medicines' broader RAS(ON) platform, around which the company has built a pipeline of multi-selective and mutant-selective inhibitors. Rasonque is the first product from that platform to reach the market, giving the company a commercial foothold as it advances follow-on RAS-targeted programs and expands daraxonrasib into earlier treatment settings. Rasonque enters a pancreatic cancer market where targeted therapies have previously been limited to relatively small molecularly defined subsets, including patients with germline BRCA mutations or NRG1 fusions. Its lack of a mutation-specific selection requirement therefore substantially broadens the potential reach of targeted treatment compared with those earlier approaches. The EMA's Committee for Medicinal Products for Human Use has initiated a phased review of daraxonrasib for the same indication. Revolution Medicines has also initiated the Phase III RASolute 303 trial, evaluating daraxonrasib in the first-line setting, where success could further expand the drug's role in pancreatic cancer treatment. Spot something wrong? Report an issue with this article