Revolution Medicines said Monday that its pancreatic cancer drug daraxonrasib succeeded in a highly anticipated Phase 3 trial, meeting all primary and secondary endpoints and showing a manageable safety profile with no new safety concerns. The company said the daily pill almost doubled the typical length of survival and cut the risk of death by 60% versus chemotherapy in the trial of people whose cancer had already progressed on another treatment.
Who Gets the Benefit, Who Bears the Cost
People who took daraxonrasib typically lived for 13.2 months versus 6.7 months for people who took chemotherapy, an increase of 6.5 months, according to a company press release. That is the central fact the company is putting forward: a drug from a private firm, tested on people with advanced cancer, now being presented as a major step toward approval while the patients who entered the trial remain the ones carrying the burden of the disease and the treatment.
Revolution Medicines said it will soon seek Food and Drug Administration approval using a Commissioner's National Priority Voucher, which grants a review within a matter of months, and it plans to seek approval for second-line treatment in patients whose cancer has already spread while taking another drug. The company is also conducting a Phase 3 trial for newly diagnosed patients. The machinery of approval is moving fast now that the company has a result to sell, with the state’s drug-review apparatus set to decide how quickly this treatment can be pushed into the market.
The Company’s Pitch
Revolution Medicines CEO Mark Goldsmith said in an interview, "These are dramatic, practice-changing outcomes, and our focus now is moving quickly to bring this potential new treatment option to patients who urgently need new treatment." Goldsmith called the results "unprecedented," saying no drug has shown an overall survival benefit greater than one year in a Phase 3 trial for pancreatic cancer. He also said, "These results usher in a new era of RAS-targeted medicines for pancreatic cancer, which has been exclusively treated with cytotoxic intravenous chemotherapy."
The company said daraxonrasib broadly targets RAS mutations, which drive tumor growth and are found in about 90% of pancreatic cancer cases. Revolution Medicines said pancreatic cancer has the lowest five-year survival rate of any major cancer, at 13%.
Dr. Shubham Pant, professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, said the results are "truly transformational." Pant said he had been involved in numerous other studies that had failed and that previous positive trials extended survival by a few weeks or months. He said, "Today, I'm just, I'm just thankful. That's all I can say. And you know, just seeing patients in my clinic today, I've got a busy clinic today, and I'm just thankful." Pant said he had been involved in trials for Revolution Medicines' daraxonrasib since its early days and choked up multiple times when describing the results and what they mean for patients, including one who participated in the pivotal trial that Pant had seen just before the interview.
Side Effects, Hype, and the Approval Pipeline
Daraxonrasib gained more attention last week when former Republican Sen. Ben Sasse, who was diagnosed with pancreatic cancer late last year and given only months to live, shared his experience taking the drug in an interview with The New York Times. He told the Times that Pant is his doctor. Sasse said his tumors have shrunk 76% since he started taking the drug, but said it causes "crazy" side effects like a facial rash. His face appeared to be peeling during the interview.
Goldsmith said the company cannot comment on any individual patient, but said a rash is a known side effect and one that is generally manageable. Pant said the majority of patients in previous trials of daraxonrasib did experience a rash, though less than 10% of them developed a "dramatic" rash. He said strategies like stopping the drug temporarily or treating with antibiotics can help. Pant said, "Honestly, since our journey three years ago, we are getting better at managing these side effects, and I think we keep on getting better at managing side effects." Revolution Medicines said Monday that no new safety concerns were observed in the pivotal study and that the full results will be disclosed at a medical meeting.
Dr. Andrew Aguirre, associate director of the Hale Family Center for Pancreatic Cancer Research and co-director of the Center for RAS Therapeutics at Dana-Farber Cancer Institute, said daraxonrasib could become a foundation that can be built upon and used in combination with other drugs. He called the results a "whopping improvement" to be "incredibly excited about as really a foundation." Aguirre said, "And honestly, it's reason for optimism for the whole field that targeting RAS in this patient population, and hopefully many other contexts for pancreatic cancer and many other difficult-to-treat diseases is going to have real benefit for patients and be something that we can continue to expand and use in combination."
Revolution Medicines shares jumped more than 30% following release of the results Monday. Its stock has climbed about 274% in the last year, in part because it has long been seen as an acquisition target. Monday's stock move brought the company's market value to more than $26 billion. Goldsmith said the company is focused on preparing for approval and launch of its drug, rather than any potential acquisition.