The US Food and Drug Administration has approved a new pancreatic cancer drug, a pill that nearly doubled patients’ average survival times for one of the deadliest cancers when taken instead of chemotherapy, reports The Washington Post.
Researchers have called the drug – Rasonque or daraxonrasib and taken daily – a “landmark” development. It has been one of the most closely watched experimental cancer treatments.
In a trial of 500 adults with metastatic pancreatic cancer who had been previously treated for the condition, patients who took daraxonrasib had a median survival period of about 13.2 months, compared with 6.7 months for those who received chemotherapy.
When the trial results were presented at an American Society of Clinical Oncology meeting earlier this year, the room erupted in applause and a standing ovation. Some in the audience were in tears.
“It’s a huge game-changer for the pancreatic cancer population,” said Jad Chahoud, chief scientific and innovation officer at the Orlando Health Cancer Institute, after the FDA approval last week.
The drug, manufactured by Revolution Medicines, works by targeting a gene called KRAS, a common cancer-causing gene that regulates cell growth.
The gene, which has been associated with pancreatic, liver and colorectal cancers, has long been identified as a target for cancer treatments but has proved difficult for scientists to attack. Daraxonrasib inhibits proteins produced using KRAS, stopping the growth of cancer cells.
“That’s what makes this medicine so different from what we’ve done in the past,” said Brian Wolpin, director of the Hale Family Centre for Pancreatic Cancer Research at the Dana-Farber Cancer Institute and principal investigator for the Phase 3 clinical trial evaluating the drug. “It’s really going after the underlying biology of the disease.”
The FDA expanded access to daraxonrasib in May as it underwent review, stating that the drug met a critical need in treating pancreatic cancer, which has one of the lowest survival times among cancers.
There is no screening for pancreatic cancer, and it is often caught late, after it has already metastasised and few treatment options remain. Around 14% of patients survive five years or more after a diagnosis.
Wolpin, who oversaw patients participating in the trial, said the drug is also easier to administer and less hard on the body than chemotherapy, which can require patients to sit for hours-long infusions.
“It’s a huge difference for patients to be able to take a pill that has, generally speaking, substantially less side effects than IV chemotherapy,” Wolpin said.
The most common side effects of daraxonrasib include rash, diarrhoea, nausea, fatigue, vomiting, abdominal pain, decreased appetite and haemorrhage, according to the FDA.
Experts said the success of daraxonrasib could spur further developments in pancreatic cancer treatment, as well as other cancers associated with the KRAS gene. A trial of daraxonrasib to treat lung cancer is under way, Wolpin said.
“I think it, ultimately, will impact many different diseases,” he said.
Race to develop more
The approval marked the end of a long quest to develop a medicine that can hit one of cancer’s most elusive targets.
At least 79 treatments are currently being tested in cancers of the pancreas, lung and colon, in 238 clinical trials worldwide, according to one tally – all racing to develop similar drugs that will also attack the mutated cellular protein smooth-surfaced KRAS.
The New York Times reports that it fuels nearly all pancreatic cancers, as well as many lung and colon cancers and some other tumour types, but for years, it was considered impossible to attack, because it lacked an obvious toehold for a drug to exploit.
However, 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 Hong, an oncologist at MD Anderson Cancer Centre in Houston and one of the leaders of an early safety study of daraxonrasib.
He compared its approval to the advent about 15 years ago of immune checkpoint inhibitors, now used against a broad array of tumours.
Studies are already under way 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.
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.
Leading the charge
Revolution Medicines, a small company near San Francisco that had no approved products before daraxonrasib, is regarded 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 has won approval.
Revolution is also developing a similar medicine, zoldonrasib, that has shown early promise for lung cancer. The company also has collaborations under way with 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 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, tumours 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 human cancers, including some that have not historically been thought to be susceptible to this kind of treatment approach.
In breast tumours, for example, KRAS mutations are very rare, 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 Centre at UT Southwestern Medical Centre, 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 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 company, 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 year, 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.
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