Ben Sasse shines spotlight on daraxonrasib for pancreatic cancer

Revolution Medicines could be on the cusp of a breakthrough. 

The company expects to soon release results from a Phase 3 trial of its experimental drug that could become the first targeted treatment for pancreatic cancer, the deadliest of the major cancers. Just 13% of people with pancreatic cancer live five years after they’re diagnosed, a number that hasn’t changed much despite the outlook for other cancers improving thanks to new drugs like immunotherapy. The possibility of a new treatment has buoyed RevMed’s stock by nearly 185% over the last year and made it a prime acquisition target.

“This is incredibly important,” said RBC Capital Markets analyst Leonid Timashev. “We’ve had physicians describe this as potentially the biggest breakthrough in pancreatic cancer ever.”

RevMed came into the spotlight this week when former Sen. Ben Sasse told The New York Times he’s taking the company’s drug, daraxonrasib. Sasse late last year announced he was diagnosed with Stage 4 pancreatic cancer and given three-to-four months to live.

Sasse told the Times that his tumors have shrunk by 76% since he started the treatment, but he called it a “nasty drug” that causes “crazy” side effects like a rash. Sasse’s bloody, peeling face prompted the interviewer to tell Sasse he looks “terrible.”

RevMed’s daily pill broadly targets RAS mutations, which drive tumor growth and are found in about 90% of pancreatic cancer cases. Timashev describes RevMed’s drug as striking at the heart of what makes the cancer go.

That’s both a benefit and a liability. RAS proteins are all over the body, especially in the skin. RevMed’s drug doesn’t distinguish between the mutated version and the normal one, producing unpleasant side effects like those Sasse experienced.

RevMed in a statement said the majority of rash cases have been low grade, with no patients discontinuing treatment because of it. The company added that reports of rashes with bleeding have been described anecdotally by clinical trial investigators and are considered uncommon.

Early on, RevMed wasn’t sure people would even be able to tolerate daraxonrasib because it was so broadly active against all the different forms of RAS, said CEO Mark Goldsmith. The company started with a “very, very low dose” and gradually escalated it. 

“We fretted over every escalation,” he said. “Every time the team said we’re about to increase the dose, a senior group of us sitting in a conference room would just be holding our head in our hands thinking, ‘Is this going to be it? Are we going to be able to go higher?'”

The company’s scientists predicted that at 80 milligrams, tumors would start to shrink, Goldsmith said.

“They had done the science to predict that, and that’s exactly what happened,” he said. “We saw the first patient’s tumor shrink, and we said, ‘Wow, our team’s pretty good. They know how to predict this stuff.'” 

But showing the drug can shrink tumors likely won’t be enough to secure approval from the U.S. Food and Drug Administration. Goldsmith said the agency has been clear privately and publicly that RevMed needs to show daraxonrasib can keep people alive longer, what’s known in the medical community as demonstrating a benefit to overall survival.  

The magnitude of that benefit could have significant implications for how widely the drug will be used, and how the company’s stock will react to its late-stage data. RevMed expects to share data this quarter from a Phase 3 trial studying its pill versus chemotherapy in people whose cancer has spread and who have already tried one other treatment. 

RBC Capital Markets analysts laid out their base case in a note to clients on Friday, predicting the stock will rise between 25% and 40% if RevMed’s drug shows an overall survival benefit of more than 13 months and decreases the risk of death by half compared to chemo. The drug failing the Phase 3 trial would be an “incredible disappointment,” Timashev said, an outcome he sees as unlikely. A more likely risk, in his view, is the drug doesn’t deliver as much of a benefit as investors are expecting.

Part of the recent spike in RevMed’s stock is coming from speculation that the company will be acquired, with Merck reportedly looking at a deal earlier this year.

Goldsmith said RevMed doesn’t pay much attention to “external noise” and is focused on building the company.

“We do know pharma companies are highly interested in what we do,” he said. “They’re either trying to copy it or they’re trying to get it. And that sort of stuff will happen around us. Sometimes there will be rumors. What can we say? We’re not really focused on how do we get the company into the hands of others? We’re focused on how do we make the most difference?”