The Food and Drug Administration’s approval on Wednesday of a new drug for pancreatic cancer marked the end of a long quest to develop a medicine that can hit one of cancer’s most elusive targets.
Researchers hope the new drug is just the beginning, opening a new chapter in treatment for a range of cancer types.
At least 79 drugs that take a similar approach are being tested in 238 clinical trials worldwide, according to one tally by academic researchers.
Large drugmakers like Eli Lilly, Pfizer, Amgen and AstraZeneca are among the companies racing to develop their own medicines that work like the new drug, daraxonrasib, which is made by Revolution Medicines and will be sold as Rasonque.
The new drug, taken as two daily pills, attacks a mutated cellular protein called KRAS. It has long been an enticing target, because it fuels nearly all pancreatic cancers, as well as many lung and colon cancers and some other tumor types. But for years, the smooth-surfaced KRAS protein was considered impossible to attack, because it lacked an obvious toehold for a drug to exploit.
But a series of scientific advances gradually overturned that doctrine, showing that KRAS could be conquered. Starting around 2024, research activity in the field exploded.
“This is not just pancreatic cancer,” said Dr. David S. Hong, an oncologist at MD Anderson Cancer Center in Houston and one of the leaders of an early safety study of daraxonrasib. He compared its landmark approval to the advent about 15 years ago of a powerful class of immunotherapy drugs, called immune checkpoint inhibitors, that are now used against a broad array of tumors.
Cancer is a slippery foe that often finds a way to evade one particular therapy, and there’s hope that treating it with multiple approaches simultaneously could help squelch tumors. Already, studies are underway that test combinations of KRAS-targeting drugs alongside other types of therapies to launch a multipronged attack. Daraxonrasib’s approval could lead to more such trials.
Researchers widely agree that the emerging class of drugs “will need combinations to advance their clinical response and durability,” said Channing Der, a pioneering KRAS scientist who oversees academic labs in North Carolina and Berlin that have been tracking experimental drugs and trials in the field.
Revolution Medicines, a small company near San Francisco that had no approved products before daraxonrasib, is widely seen as the leader in the field. One of its most closely watched, and potentially most significant, trials is testing daraxonrasib as the first drug given after a pancreatic cancer diagnosis, instead of as a second-line treatment for people who had already tried chemotherapy, the group for which the drug won approval.
Revolution is also developing a similar medicine, zoldonrasib, that has shown early promise for lung cancer. The company also has collaborations underway with drugmakers like Bristol Myers Squibb, Tango Therapeutics and Summit Therapeutics to study combinations involving its KRAS-targeting drugs.
Daraxonrasib is not the first to target KRAS. Two others, sold by Amgen and Bristol Myers Squibb, won approval to treat forms of lung cancer several years ago. But those drugs were disappointments. They delivered only modest benefits, because they targeted only one mutant form of KRAS, and only when it was not actively driving cancer growth. As a result, tumors rapidly mutated to evade the treatment.
Drugs like daraxonrasib and others in development are more powerful because they can work on an array of mutations, and because they block KRAS when it is actively causing cancer growth. But they run into the same problem as other targeted therapies; eventually, the treatment stops working and the cancer returns.
KRAS is part of a family of proteins that develop mutations in about a fifth of human cancers, including some that have not historically been thought to be susceptible to this kind of treatment approach.
Take breast cancer, for example. KRAS mutations are very rare in breast tumors , but when the breast cancer spreads to other parts of the body, like the lungs or the liver, and develops a resistance to treatment, it can sometimes develop KRAS mutations.
Researchers now hope to plan a clinical trial that would test the approach in breast cancer, said Ariella Hanker of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, one of the scientists involved in the work.
Dr. Elizabeth Jaffee, a pancreatic cancer researcher at Johns Hopkins, listed some of the most pressing needs in the field: Creating a new generation of KRAS-targeting drugs with fewer side effects; finding ways to overcome the resistance that allows cancer to surge back; and combining KRAS-targeting drugs with other treatments, including those that harness a patient’s immune system to attack cancer.
“We’re all really excited, of course,” she said. But, she added, “we have a lot to do.”
Achieving those goals will require close collaboration between companies with competing interests, she said. And in one case, tensions have already crept into public view.
One drugmaker, Erasca, has generated attention for early stage studies of its KRAS-targeting drug, ERAS-0015, in cancers of the lung and pancreas. That experimental drug is similar to daraxonrasib — so similar, in fact, that, in a letter last spring, Revolution Medicines’s lawyers accused its competitor of violating a key patent, and demanded that it stop work on the drug in the United States. Erasca, which is based in San Diego and bought the rights to its experimental drug from a Chinese company, has denied the accusations.
