Shortly after locking down a world-first approval in China, Bayer is bringing its groundbreaking stroke prevention drug stateside, with an FDA green light that honors the German drugmaker’s cardiovascular heritage and signals the sort of first-in-class opportunities it’s increasingly seeking.
The FDA on Nov. 9 signed off on Bayer’s factor XIa inhibitor asundexian, ushering in one of the first major revolutions in stroke prevention in decades. The approval enables Bayer to market the once-daily oral medicine under the brand name Sunharbo in combination with antiplatelet therapy to reduce the risk of stroke in adults with a recent non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA).
That label echoes the indication Sunharbo won from China’s National Medical Products Administration in late October, marking the first approval worldwide for a drug in asundexian’s factor XIa inhibitor class.
Some 87% of all strokes are ischemic, and 80% of ischemic strokes are non-cardioembolic, Sebastian Guth, chief operating officer of Bayer Pharmaceuticals and president of Bayer U.S., said in an interview, putting Sunharbo’s approved population into context.
“Stroke remains a very significant health burden in the United States, and the need for continued innovation is abundantly clear,” Guth emphasized. According to the Centers for Disease Control and Prevention, stroke is the fourth-leading cause of death and a leading cause of disability in the U.S., with some 795,000 Americans experiencing a stroke each year.
Meanwhile, roughly 1 in 10 ischemic stroke survivors will experience another stroke within a year, and 1 in 5 will experience another within five years. The psychological toll that fears of another stroke can take not only on patients but also on their caregivers and families can be immense, the Bayer executive said.
Despite the unfortunate prevalence of second stroke events, the recurrence rate of stroke hasn’t shifted in the past 20 years, which Guth flagged as a clear sign of the need for novel approaches to prevention.
The FDA go-ahead leveraged data from Bayer’s OCEANIC-STROKE study, which also paved the way for the recent China approval and tied asundexian to a 26% reduction in ischemic strokes. And in a crucial win for asundexian’s safety, Bayer’s drug charted these results without increasing major bleeding, which affected 1.9% of patients on the study drug compared with 1.7% of those on placebo.
For Bayer, the asundexian nod marks a major shift in a field it’s already intimately familiar with, having made a name for itself in the cardiovascular, cerebrovascular and thrombotic arenas with drugs like rivaroxaban (Xarelto).
Crucially, the green light is also a testament to a shift in Bayer’s development strategy in recent years, which has seen the German drug giant increasingly turn its attention toward “first- and best-in-class medicines,” Guth said.
The lack of innovation prior to asundexian largely comes down to a tricky risk-benefit calculus, Christoph Koenen, M.D., Bayer’s chief medical officer, said during the interview.
He noted that while “other antithrombotic drugs have tried to show an effect in secondary stroke prevention, the problem with previous intervention was always the fact that the risk-benefit simply didn’t support use in this patient population,” pointing again to major bleeding episodes, which he described as the “biggest concern,” side effect-wise, in stroke patients who go on to receive an anticoagulant.
In tracing Bayer’s R&D path to the factor XIa well, Koenen harkened back to Bayer’s history of work in anticoagulation, name-checking Xarelto in particular. The thesis for factor XI inhibition itself comes from the desire to prevent the formation of “bad clots” during the coagulation cascade, while at the same time interfering “as little as possible with a natural repair mechanism” the body needs for various functions, like sealing vascular tears to avoid bleeding, Koenen explained.
The other ingredient in the secret sauce behind factor XI inhibition was “genetic evidence,” the CMO said. Patients with certain genetic mutations that give them lower levels of factor XI from birth also have lower rates of cardiovascular events like heart attack and stroke, Koenen explained, which gave researchers “reason to believe that lowering factor XI in humans actually has the desired antithrombotic effect.”
It was the wedding of those pieces that made factor XI “such an interesting target to pursue,” said Koenen, caveating that the journey hasn’t been easy by any stretch.
The field of factor XIa inhibition hasn’t been without its stumbles, and asundexian itself has experienced its fair share, alongside its chief rival from Bristol Myers Squibb and J&J, milvexian.
Back in 2023, Bayer halted a late-stage study of asundexian in patients with atrial fibrillation after an interim peek at the data suggested the drug was less effective than Eliquis. And last November, J&J and Bristol also stopped a phase 3 trial of their still-experimental milvexian early in patients with acute coronary syndrome, citing futility.
Stroke has the potential to be an entirely different story, however, and doctors may already be champing at the bit for a new option in the prevention armamentarium.
While the factor XIa inhibition pathway has faltered in several other related indications, milvexian is also awaiting results from a phase 3 trial in secondary stroke prevention, where it may have a better shot at making it to market and eventually challenging Bayer’s Sunharbo.
Based on conversations with neurologists, not just in the U.S. but globally, Bayer figures that “asundexian has the potential to change the standard of care and be paradigm-changing in this disease state,” Guth suggested.
While the company could not yet go into specifics around asundexian’s U.S. launch prospects, Guth stressed that Bayer is ready for a rollout at scale, buoyed by concerted efforts in recent years to step up the company’s presence in the United States.
Meanwhile, as other key projects play out across the company’s U.S. network, Bayer today is “well placed” with an established commercial team, a strong medical team and “all of the required support infrastructure” for a successful Sunharbo debut, Guth said.