FDA approves first RAS-targeted drug for metastatic pancreatic cancer

The Food and Drug Administration on Wednesday approved Rasonque, the first RAS-targeted drug ever cleared for metastatic pancreatic cancer, a disease that kills more than 50,000 Americans a year and has long resisted the kind of targeted therapies that transformed treatment for other cancers. The once-daily pill, known chemically as daraxonrasib, is made by the California biotechnology company Revolution Medicines.

The drug is approved for adults with metastatic pancreatic adenocarcinoma who have already had at least one round of systemic therapy, or who are not candidates for standard multi-agent chemotherapy. Unlike earlier RAS-targeted cancer drugs, it works regardless of which specific RAS mutation a patient carries and does not require a companion diagnostic test to confirm eligibility — a distinction oncologists say matters because more than 90 percent of pancreatic tumors are driven by mutations in the RAS family of genes.

The numbers behind the approval

The FDA's approval rests on results from the Phase 3 RASolute 302 trial, which enrolled 500 patients across North America, Europe and Asia. Patients on daraxonrasib had a median overall survival of 13.2 months, compared with 6.7 months on standard chemotherapy — roughly a 60 percent reduction in the risk of death. Median progression-free survival was 7.2 months versus 3.6 months, and 31.6 percent of patients saw their tumors shrink or disappear, compared with 11.2 percent on chemotherapy. Revolution Medicines said in its own investor announcement that the trial data were presented earlier this year to a standing ovation at a major oncology conference.

Pancreatic cancer is diagnosed in roughly 65,000 Americans annually, and about 80 percent of cases are found only after the disease has already spread. Five-year survival for metastatic disease sits at around 3 percent, among the lowest of any major cancer, according to figures cited by the advocacy group Pancreatic Cancer Action Network.

An accelerated path, and a real price tag

The drug moved through the FDA on an unusually fast track, carrying Breakthrough Therapy, Orphan Drug and Priority Review designations, along with the agency's new Commissioner's National Priority Voucher pilot program, which compressed the review timeline to roughly one to two months and delivered the approval more than six months ahead of the standard statutory deadline. An expanded-access program had already been supplying the drug to some patients outside the trial since May.

Revolution Medicines set the list price at $39,800 for a 30-day supply and said the drug is now commercially available by prescription. The company has launched a patient-support program, called (ON)_Path, to help patients navigate insurance coverage and financial assistance.

The safety profile is significant: 86 percent of patients experienced some skin-related side effect, 63 percent had diarrhea and 57 percent developed mouth sores, most cases mild to moderate. More serious risks include gastrointestinal perforation, which occurred in 0.9 percent of patients and was fatal in one case, and inflammatory lung disease, also fatal in one case. The drug's label carries a warning about harm to a developing fetus.

Reaction from researchers and patients' advocates

"The FDA approval of daraxonrasib represents a landmark advance for patients with metastatic pancreatic cancer," said Dr. Brian Wolpin of the Dana-Farber Cancer Institute, one of the research centers involved in the drug's development.

Dr. Benjamin L. Ebert, chief executive of Dana-Farber Cancer Institute, said the Boston research center was "proud to have helped lead preclinical and clinical research that made this advance possible." Dr. Anna Berkenblit, chief scientific and medical officer at the Pancreatic Cancer Action Network, called the approval "the most significant advance we have seen in the fight against pancreatic cancer, a devastating disease." Revolution Medicines chief executive Mark Goldsmith described it as "a monumental step forward for patients with pancreatic cancer and for the oncology field."

Earlier RAS-targeted drugs from Amgen and Bristol Myers Squibb were limited to tumors carrying a single specific mutation, KRAS G12C, and only in its inactive molecular state — a narrow slice of cancers overall and an especially small one in pancreatic disease, where that particular mutation is uncommon. Researchers say daraxonrasib is distinguished by blocking multiple active forms of RAS proteins broadly, which is why it does not require genetic pre-screening to determine eligibility. RAS genes had been considered essentially "undruggable" for decades because the proteins they produce lack an obvious pocket where a small-molecule drug can bind; it took roughly ten years of work across several biotech and pharmaceutical labs to design compounds able to interfere with RAS activity at all, let alone across its many mutated forms.

Part of what has made pancreatic adenocarcinoma so lethal is timing: because the pancreas sits deep in the abdomen and early symptoms are vague — mild back pain, weight loss, a change in appetite — the disease is rarely caught before it has already metastasized. Standard treatment for metastatic disease has for years relied on multi-drug chemotherapy regimens that are difficult for patients to tolerate and offer only modest survival gains. Combined with the tumor's unusually dense, fibrous structure, which can block drugs from reaching cancer cells, pancreatic cancer has seen far less improvement in outcomes over the past two decades than cancers such as melanoma or certain lung and blood cancers, where targeted and immune therapies have meaningfully extended survival.

What happens next

Oncologists expect the drug to quickly become a standard second-line option for metastatic pancreatic cancer, though its real-world adoption will depend heavily on how insurers respond to its price. Revolution Medicines and its research partners are already running additional trials testing daraxonrasib earlier in treatment and in combination with other therapies, results that could determine whether its benefit extends to patients who are diagnosed before the cancer has spread.