The U.S. Food and Drug Administration has approved daraxonrasib, a groundbreaking therapy for advanced pancreatic cancer, marking a significant milestone in the treatment of one of medicine’s most challenging malignancies.
Administered as two daily pills, this novel treatment represents the first drug to meaningfully extend survival for patients with metastatic pancreatic cancer. While not a cure, daraxonrasib has demonstrated unprecedented efficacy in clinical trials.
Developed by Revolution Medicines and marketed under the brand name Rasonque, the drug targets patients who have progressed after chemotherapy. In pivotal trials, patients receiving daraxonrasib survived a median of over 13 months, compared to just under seven months for those on standard chemotherapy. Some trial participants have experienced survival extending several years.
“We’ve never witnessed benefits of this magnitude in pancreatic cancer before,” stated Dr. Anna Berkenblit, chief scientific and medical officer at the Pancreatic Cancer Action Network.
The drug’s list price is set at $39,800 monthly, approximately $478,000 annually, though most costs are anticipated to be covered by insurance with variable patient co-pays.
Since May, over 2,000 patients have accessed the medication through the company’s expanded access program following positive trial outcomes. These patients will transition to insurance coverage moving forward.
The FDA granted approval just 35 days after accepting the application, following designation for expedited review.
Pancreatic cancer, which claims over 50,000 lives annually in the United States, remains among the deadliest cancers, with only 3% of metastatic patients surviving five years post-diagnosis. Traditional chemotherapy offers limited life-extending benefits.
At a recent medical conference in May, oncologists reportedly applauded and some wept upon seeing trial data demonstrating doubled survival times.
Dr. Brian Wolpin of the Dana-Farber Cancer Institute, lead researcher on the pivotal study, described being amazed by the results when he first reviewed them. “I haven’t observed anything comparable in our pancreatic cancer research,” he noted, adding that he repeatedly expressed amazement at the findings.
Nearly all pancreatic cancers, along with many lung and colorectal malignancies, depend on a mutated protein known as KRAS for growth and survival. Previous attempts to develop drugs targeting this protein were deemed futile due to its smooth molecular surface offering no clear binding sites.
However, decades of research breakthroughs dismantled this prevailing skepticism. Daraxonrasib’s success validates that KRAS can indeed be therapeutically targeted through an innovative mechanism that combines molecules to bind and inhibit the protein.
Dr. Kevan Shokat of the University of California, San Francisco, whose 2013 discoveries helped overturn assumptions about KRAS drugability, co-founded Revolution Medicines as both academic consultant and scientific advisor.
During a morning workout recently, Dr. Shokat received numerous congratulatory messages celebrating the drug’s approval. “I’m absolutely thrilled,” he said upon learning of the validation.
Common side effects include rash, diarrhea, fatigue, and nausea. Some clinical trial participants reported severe reactions, with others expressing desire for even longer survival periods to spend additional time with loved ones.
Nonetheless, promising early results over recent years sparked intense interest in clinical trials globally.
Dr. Nilofer Azad, a pancreatic cancer specialist at Johns Hopkins, noted receiving daily inquiries worldwide regarding clinical trial participation opportunities for daraxonrasib.
Among the most notable cases involves former Nebraska Senator Ben Sasse, who publicly disclosed his metastatic pancreatic cancer diagnosis in December 2022 and credited daraxonrasib with significantly reducing his tumor markers.
Medical professionals view daraxonrasib as merely the beginning of what they anticipate will become an entirely new treatment paradigm for pancreatic and other KRAS-driven cancers. Multiple pharmaceutical companies are currently evaluating complementary KRAS inhibitors across various combinations with existing treatments, including immunotherapies.
Future aspirations include achieving long-term disease management or potentially indefinite remission for most patients.
Despite progress, numerous questions persist according to Revolution Medicines CEO Dr. Mark Goldsmith during a recent webinar discussion.
“What determines how long tumors take to regress?” he questioned. “Why don’t they respond immediately? What remains after aggressive therapeutic intervention?”
He also pondered why select individuals achieve complete tumor elimination while taking daraxonrasib.
Jerry Simonson, 79, residing near Salt Lake City, exemplifies such exceptional responses.
Initially misdiagnosed during a shoulder infection consultation in 2017, his cancer had already spread to lymph nodes by discovery.
Facing grim prospects, Mr. Simonson anticipated limited survival expectations based on previous acquaintances’ experiences. “I told myself I had maybe two months left,” he recalled.
Participating in a late-stage clinical trial beginning December 2022, he observed rapid tumor reduction leading to undetectable scans today. Maintaining good health, he walks two miles daily and recently took up pickleball, experiencing minimal side effects effectively managed through topical treatments.
Previously unaware of the drug’s significance, he only fully grasped its revolutionary impact upon seeing national coverage from the May conference. “That moment made it real for me,” he reflected.
-
This is great news for patients. Also a good opportunity to mention that’s there are clinical trials with exceptional results obtained with personalized mRNA vaccines (which work in a way analogous to the melanoma vaccine reported last week).
Rebecca Robbins
Pharmaceutical reporter
-
Great news. But why would it only be available for people who have already tried chemotherapy? Surely anyone with a pancreatic cancer diagnosis would want to try this new drug right away. I say this as someone who’s seen many friends, and a couple of extended family members, die of this disease. Some in their 40s.
Gina Kolata
Health reporter
@CitizenJ the clinical trials showing the drug is effective were restricted to people who had had chemotherapy. The drug is being studied now earlier in the course of the disease
