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At 69 years old, Debby Orcutt was diagnosed last year with pancreatic cancer, a condition so dire that her doctor refused to tell her how long she had to live. With few good options, she enrolled in a clinical trial for an experimental drug.
"I just looked at it like, what have I got to lose?" she said. "I'm gonna die."
A recent scan showed her tumor had shrunk 64 percent since starting the drug in January, according to her husband. It is the sort of clinical evidence that is stirring optimism and has prompted the Trump administration to put it on a novel path for rapid approval. Orcutt, a grandmother and retired dental assistant, said she wakes up every day at her home near Worcester, Massachusetts, feeling fine.
Based on early clinical trial results, the Food and Drug Administration in October awarded the drug's sponsor, biotech company Revolution Medicines, a new and unconventional accelerated review designed to get promising drugs to patients faster than ever. The pancreatic cancer drug, and other medications selected under the "Commissioner's National Priority Voucher" initiative, will test whether it can expedite novel treatments without compromising the rigor of agency reviews, experts say.
The FDA has said the program can shorten the review of a drug from a year to as little as a month, enabling companies that win the agency's approval to sell a medication sooner.
The agency also gave vouchers to drugs for infertility, Type I diabetes, nicotine vaping addiction, deafness, blindness and a rare blood disorder, along with ketamine for anesthesia and domestic manufacturing of an antibiotic.
Dan Kracov, a partner at Arnold & Porter who has advised multiple companies that have received a voucher, said the FDA's goal of far faster review times for certain drugs appears feasible given the program's limited scope. But it could strain agency resources, he added, depending on how much it expands.
"It's something that needs to be watched carefully to make sure you're not lowering the standards so much to get a product on the market that you're compromising patient safety," he said.
Andrew Nixon, a spokesman for the Department of Health and Human Services, said the FDA will always maintain rigorous standards and that the new voucher program will reduce "idle time."
The FDA's selection of Revolution Medicines' daraxonrasib appeared to cement its status as one of the most promising experimental cancer drugs. It also is being studied for treating lung and colorectal cancer.
One of the company's first clinical trials gave daraxonrasib to 83 patients whose pancreatic cancer had spread after undergoing at least one earlier intervention, such as chemotherapy. Over more than 16 months, at least 29 percent of the participants saw their tumors shrink while more than 90 percent saw no tumor growth. The median overall survival was 15.6 months, according to the results, which by some measures is about twice as long as such patients typically fare with standard treatments. Results of its first major, randomized trial, with about 460 patients, are expected next year.
Investors have pushed the company's stock-market value above $10 billion, making it an outlier even among the often-lofty valuations of early-stage biotech companies. Revolution Medicines, which went public in 2020, does not have any drugs on the market and has racked up more than $2 billion in losses since its founding in 2014.
The need for a drug to treat pancreatic cancer is especially urgent. It is the third-leading cause of U.S. cancer deaths, according to the National Cancer Institute, and among the most lethal. The five-year survival rate for pancreatic cancer is only 13 percent, and for those whose cancer has spread to other parts of the body, it falls to 3 percent. The standard treatments, along with the death rate, have remained largely unchanged for the past 30 years.
But the science behind daraxonrasib and similar drugs in development is fueling new hope.
"I think this is the turning point for the field of pancreatic cancer," said Brian Wolpin, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and an investigator in multiple clinical trials for daraxonrasib. Though he cautions that the data hasn't yet been validated in a randomized trial, he's been struck by how daraxonrasib has shrunken tumors and alleviated patients' abdominal pain.
The drug "feels like the foundation on which we can really build effective treatments," Wolpin said.
It is not, however, without significant side effects. In a trial of 40 participants receiving daraxonrasib as an initial treatment for pancreatic cancer, 95 percent reported an undesirable reaction and 35 percent suffered a severe one, according to company data. The most common side effect is a skin rash, which generally wasn't debilitating.
And for all its promise, the drug isn't a cure. Lei Zheng, an oncologist and member of the American Pancreatic Association, expressed hope that daraxonrasib can be improved to suppress cancer for longer, with ongoing studies to determine how patients develop resistance to the drug.
Revolution Medicines' scientists decided early on to focus on a family of genes that work like a kind of switch for directing cells to divide and grow. Mutations of RAS genes, as they're known, create mutated proteins that effectively get stuck in the "on" position, sending a signal for cancer cells to proliferate.
The company's drug targets mutant proteins that for years had eluded efforts to neutralize them, with their smooth surfaces leaving no obvious pocket where a drug could be attached. In 2013, a team led by Kevan Shokat - a University of California at San Francisco professor who would become a co-founder of Revolution Medicines - created a novel way of stopping one of these proteins from signaling cancer cells to keep growing. Revolution Medicines then searched for a compound that blocks the growth signals from the majority of such proteins.
"That was a heretical idea," Mark Goldsmith, Revolution's CEO, said in an interview. The prevailing view then among scientists was that broadly turning off that growth signal would affect normal cell growth and harm patients, he said.
In animal trials, scientists were surprised that it shrank tumors without the toxicity they'd braced for. "We did this experiment over and over because it ran so much against dogma we knew that we had to be sure we were right," Goldsmith said.
Anna Berkenblit, chief scientific and medical officer of the Pancreatic Cancer Action Network, said she was excited to see the FDA award the new priority voucher to Revolution Medicines, calling its experimental drug "a fundamental game changer." The wave of drugs targeting RAS mutations, she said, is "quantum-leap different" over existing therapies.
The FDA has a long history of expediting its reviews of promising cancer treatments, with mixed results.
From 2012 to 2021, cancer drugs accounted for more than 80 percent of all drugs that received the FDA's accelerated approval, in which companies have to show only that their drugs are likely to benefit patients rather than demonstrating actual benefit, such as longer survival, according to a 2024 JAMA paper.
While some studies suggest this flexible approach has been a success, the JAMA paper cited drawbacks: Among 46 approvals between 2013 and 2017, 41 percent did not demonstrate a benefit in overall survival within five years of getting accelerated approval and no results were available for an additional 15 percent, the authors found.
Other research examining the years 2010 to 2019 found that the FDA's median review time for cancer drugs that received accelerated approval was 179 days.
In announcing the new voucher program in June, FDA Commissioner Marty Makary said it would speed up decisions by allowing drugmakers to submit most of their application before completing their final clinical trials. Makary, a surgical oncologist, likened the approach to his experience making life-and-death decisions with a multidisciplinary "tumor board" in a day-long discussion.
Unlike other accelerated review efforts the agency has launched, the new program doesn't come with detailed guidance on its inner workings. The program's criteria are broad and cite national priorities that traditionally fall outside of the FDA's mandate, including "onshoring drug development and manufacturing" and "increasing affordability" of drugs.
"We are going into the pipeline, talking to the reviewers, asking them, ‘What do you think may potentially look amazing?' " Makary said on an FDA podcast in October. In daraxonrasib's case, he said, the agency's oncology division was "enthusiastic" about the drug's potential.
A top FDA official said he raised concerns about the legal basis for the new voucher program to explain why he resigned, which came as the agency scrutinizes his criticism of a pharmaceutical firm.
Patients are beginning to learn how much time daraxonrasib can buy them. Pranathi Perati, a molecular biologist in Northern California, started taking the drug in 2023 after undergoing treatments that couldn't keep the cancer in check. For two years, it kept the tumors from spreading, enabling her to live a largely normal life and realize her goal of seeing her youngest son start college.
But she stopped taking the pills in September after her cancer began to spread, with her doctors determining she had likely developed a resistance to the medication.
Perati recently enrolled in another clinical trial for a drug that works differently, designed to track down and destroy cancerous cells based on a malignancy's particular protein signature.
Now 55, Perati is surprised to still be alive. "Every year has been a bonus," she said.