A scan last week 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. She’s debating her daughter over whether she’s well enough to host Thanksgiving.
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 reviewtimes for certain drugsappears feasible given the program’s limited scope. But it could strain agency resources, he added, depending on how much it expands.
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.
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.
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,Source comment 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.