ESC 2022: Bayer, like its rivals, hopes it made a big enough splash after phase 2 belly flop

The race to develop an anticoagulant that could better prevent secondary strokes is heating up, or cooling down, depending on how you look at it. The state of play is now clearer than it was a few days ago, after dueling Big Pharmas presented new phase 2 data.

Bayer joined rivals Bristol Myers Squibb and Johnson and Johnson in presenting phase 2 data of its factor XIa inhibitor Sunday at the European Society of Cardiology, but like its competition, asundexian failed. The company reported that the med did not produce a dose-dependent reduction in the composite rate of covert brain infarction or ischemic strokes. 

Compared to the comparator group, asundexian-treated patients had higher rates of either ischemic strokes or covert brain infarction except for in the 10mg dosing group, which notched a very slight decline of 0.2 percentage points. The phase 2 randomized 1,808 patients once-daily asundexian 10mg, 20 mg, 50 mg or placebo on top of usual antiplatelet therapy.

In a post-hoc analysis looking at recurrent ischemic strokes or transient ischemic attacks, the 50mg dose stood out, with 5.4% of patients reporting one of those events compared to 8.3% among the placebo group. And a further analysis of a subset of patients found a larger reduction depending on certain characteristics.

For example, patients with large artery stroke had a stronger response, with 9% of treated patients reporting an ischemic stroke or transient ischemic attack compared to more than 15% in the comparator arm. Among patients with extra plaque build-up in arteries that supply blood to the brain, known as atherosclerosis, 3.1% treated with asundexian had either an ischemic stroke or ischemic attack compared to 8.1% for those in the placebo group. 

“The results of PACIFIC-Stroke indicate that the potential of asundexian to prevent stroke in selected patients should be investigated further,” said study author Ashkan Shoamanesh, M.D., an associate professor of medicine at McMaster University, in a press release. 

The data join BMS and J&J's partnered med milvexian, which was released within an hour of Bayer's. The phase 2 milvexian study similarly failed its composite endpoint but had a 30% relative risk reduction in ischemic strokes among three out of five dosing groups. There were no fatal bleeding events among any of the patients including those in the placebo group, but the rate of major bleeding among milvexian-treated patients was equal to or greater than that in the placebo group.

Bayer also touted no “significant” increase in major bleeding events. All of the three asundexian dosing groups reported an increase in major bleeding events compared to placebo and all, but one—the 10mg group—reported an increase in all bleeding events.

Taken together, the company remains bullish that there’s an opportunity for asundexian to carve out a path to market. The company has already launched two phase 3 trials—dubbed "Oceanic"—that's slated to recruit some 30,000 patients total.  

“The promising results from this phase 2 trial require validation in an adequately powered phase 3 randomized trial before being applied to clinical care for secondary stroke prevention,” said Shoamanesh.