FDA Approves First RAS Inhibitor for Previously Treated Pancreatic Cancer

The Food and Drug Administration on Wednesday approved Rasonque (daraxonrasib), a once-daily tablet that blocks RAS proteins, for adults with metastatic pancreatic adenocarcinoma who have had at least one earlier systemic therapy or are not candidates for multi-drug chemotherapy. The agency called it a first-in-class targeted therapy. The sponsor is Revolution Medicines, Inc.

The approval rests on a randomized, open-label, multicenter trial of 500 adults whose metastatic pancreatic adenocarcinoma had already been treated, the FDA said. Median overall survival was 13.2 months with daraxonrasib, against 6.7 months with standard chemotherapy. In an open-label study, patients and doctors know which treatment is given, which can influence some measures; survival is less open to that bias.

Angelo de Claro, director of the FDA’s Oncology Center of Excellence, said the drug “showed unprecedented results in an area of high unmet need.” Acting FDA Commissioner Kyle Diamantas said the approval “provides a critical new option” for patients, according to the agency’s statement.

About 67,000 new pancreatic cancer cases are diagnosed in the United States each year, the FDA said. Adenocarcinoma makes up roughly 90 to 95 percent of them and about 3.2 percent of all cancer diagnoses, yet it causes a disproportionately large share of cancer deaths.

Revolution Medicines announced a one-month supply will cost about $39,800, the AP reported. The AP said patients on the drug had fewer severe side effects than those on chemotherapy. The American Cancer Society estimates about 67,000 new U.S. pancreatic cancer cases this year and more than 52,000 deaths, with a five-year overall survival rate of 13 percent, according to the AP.

Outside specialists welcomed the approval while stressing its limits. Dr. Andrew Coveler of the Fred Hutch Cancer Center told the AP, “This is one of the most anticipated approvals I can think of,” and added that the medicine “is not a cure but a significant improvement.” Dr. Pashtoon Kasi of City of Hope Orange County said it “has opened doors for many other companies.” Dr. Brian Wolpin of Dana-Farber Cancer Institute told ABC News the approval is “an exceptional moment for patients with pancreatic cancer.”

The FDA listed the most common side effects as rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite and hemorrhage. The drug is taken once daily.

The drug was reviewed under the Commissioner’s National Priority Voucher pilot program and received Breakthrough Therapy, Orphan Drug and Priority Review designations. The FDA said the approval came 6.5 months before the user-fee deadline. In May, the agency issued a “safe to proceed” letter for an expanded-access protocol that let some patients receive the drug before approval.

The survival result comes from the agency’s announcement and from a company-funded trial, the Associated Press noted. The drug is not a cure, one specialist told the AP.