FDA clears daraxonrasib after trial doubles pancreatic cancer survival

The U.S. Food and Drug Administration approved daraxonrasib on 26 August for adults with metastatic pancreatic adenocarcinoma who have already had at least one systemic treatment, or who cannot take multi-agent chemotherapy. Revolution Medicines will sell the daily pill as Rasonque. A 30-day supply is priced at about $39,800 in the United States. The company said assistance programmes will sit beside that list price.

The National Cancer Institute counts roughly 67,000 new pancreatic cancers in the United States each year. Between 90 and 95 percent are adenocarcinomas. The disease is about 3.2 percent of new cancer diagnoses and a much larger share of cancer deaths, because it is usually found late and because older drugs have moved survival only in small steps.

The approval rests on RASolute 302, a randomised, open-label, multicentre trial of 500 adults with previously treated metastatic disease. Brian Wolpin of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute led the work. In the overall population, median overall survival was 13.2 months on daraxonrasib and 6.7 months on standard chemotherapy. The hazard ratio was 0.40, with a 95 percent confidence interval of 0.30 to 0.53. Median progression-free survival was 7.2 months against 3.6 months. The objective response rate was about 30 percent against 11 percent.

Those numbers are not a cure. They are the first clear doubling of median survival in this setting with a targeted tablet. RAS proteins drive tumour growth in more than 90 percent of pancreatic adenocarcinomas. Drugmakers spent decades failing to lock the protein in its active form. Daraxonrasib is a multi-selective RAS(ON) inhibitor. It acts as a molecular glue with cyclophilin A and blocks RAS signalling across several mutant forms, including G12. Among patients with a known RAS G12 mutation, 33.2 percent on the drug had substantial tumour shrinkage, against 11.8 percent on chemotherapy.

The recommended dose is 300 milligrams by mouth once a day until the disease progresses or the side effects become unacceptable. The label warns about skin and soft-tissue toxicity, stomatitis and other mouth problems, diarrhoea, gastrointestinal perforation, interstitial lung disease or pneumonitis, and harm to a fetus. Skin rash, mouth sores and digestive trouble were the common complaints in the trial. The FDA still judged the survival gain large enough to outweigh those risks in a population with few options.

Angelo de Claro, director of the FDA Oncology Center of Excellence, called the results unusual for this disease and noted that the review finished 6.5 months before the user-fee deadline. The drug had Breakthrough Therapy and Orphan Drug designations. The file also moved through Project Orbis, which lets partner regulators review an oncology application at the same time as the FDA.

Mark Goldsmith, chief executive of Revolution Medicines, said the approval closed more than a decade of work aimed at RAS-driven pancreatic cancer. Demand jumped in April when the company first published the trial numbers. Oncologists who treated patients on the study have described people living for years rather than months. That is anecdote until larger follow-up arrives. What the 500-patient file already shows is a hazard ratio of 0.40 on death and a doubling of the median clock.

Cost will shape who actually takes the tablet. At $39,800 a month, a median 13-month course would run into the mid-six figures before discounts. Insurers, Medicare and hospital formularies now have to decide how to place a first-in-class RAS blocker against older chemotherapy that costs less and extends life half as long. Revolution Medicines said it will offer assistance. That sentence does not settle the bill.

The biology is the part that will travel. If a glue that holds RAS off-signal works in the pancreas, the same chemistry will be tested in other RAS-heavy tumours. For patients who have already been through one line of treatment, the practical change is narrower and more immediate. They now have a daily pill that, in a controlled trial, added about six and a half months to the middle of the survival curve.