- Bristol Myers Squibb and Johnson & Johnson plan to advance their closely watched, experimental blood thinner milvexian into late-stage testing despite reporting mixed results in a Phase 2 trial.
- Data presented at a medical meeting in Europe on Sunday show milvexian failed its main study goal, as it didn’t have a dose-dependent ability to reduce the risk of symptomatic ischemic strokes and MRI-detected brain lesions in patients who previously had a stroke. The partners reported a 30% risk reduction versus placebo when evaluating three of the doses against only symptomatic strokes, however, a strong enough sign for them to move forward.
- The results, combined with similarly mixed data from Bayer’s rival drug asundexian, raise doubts about the prospects of medicines known as Factor XI inhibitors that are meant to be just as effective, but safer, than blockbuster treatments like Eliquis and Xarelto. Yet multiple drugs are now in Phase 3 testing. Bayer on Sunday said it is starting a Phase 3 trial, joining a treatment from Anthos Therapeutics.
Factor XI inhibitors have become some of the most closely watched drug prospects in cardiovascular research in recent years. Their potential to prevent strokes, with a lower risk of bleeding than Eliquis and Xarelto, has led a number of drugmakers to advance programs in lockstep.
But Eliquis and Xarelto are a high bar to clear. Known as Factor Xa inhibitors, they’re strongly effective at preventing strokes in patients with atrial fibrillation. Both will lose patent protection this decade, too, meaning new, lower-cost alternatives could emerge just as Factor XI blockers are finishing clinical testing.
Nonetheless, Bristol Myers, J&J and Bayer each see the chance for Factor XI inhibitors to fill an important need. The Phase 2 trials they each reported on involved patients who have already suffered a stroke and thus can’t receive anticoagulants because of the higher risk of bleeding. Factor XI blockers are seen as potentially helpful because people who lack the clotting factor tend to not have strokes or spontaneous bleeding.
In their study, Bristol Myers and J&J enrolled 2,366 patients who had suffered a stroke or a transient ischemic attack that put them at high risk of a stroke. They were given either a placebo or one of five doses of milvexian within 48 hours — 25mg daily or 25mg, 50mg, 100mg or 200mg twice a day — with the 200mg dose arm added after the safety of lower doses was established. All patients received dual antiplatelet therapy, aspirin and the blood thinner clopidogrel for the first 21 days, followed by only aspirin.
The drug failed its primary goal, a composite measure of risk reduction that included both symptomatic strokes and the small lesions, known as covert brain infarcts, that are picked up on an MRI scan. Bayer, in a separate trial, also reported asundexian failed to hit a similar study endpoint.
Yet Bristol Myers and J&J, as well as Bayer, are pointing to an apparent effect on strokes. Bristol and J&J, for instance, noted that three of the dose levels tested — 25mg, 50mg and 100 mg twice daily — showed a 30% risk reduction in symptomatic strokes compared to placebo. Bayer, in its trial, said asundexian lowered the risk of strokes by 20%, according to a note from SVB Securities analyst David Risinger.
Bristol Myers and J&J also reported that no patients in the study suffered fatal bleeding, and there was no significant increase in symptomatic intracranial hemorrhages for any treated patient group. These bleeding risks were low and in line with Phase 2 study results in patients who’d had knee replacement surgery, lead study investigator Mukul Sharma, Director of the Stroke Program at McMaster University, said in an interview.
“We are very excited about these results,” he said. “There are a couple of doses that deserve further study in phase three, which really will prove the efficacy.”
Risinger agreed that while the data for both milvexian and asundexian were both mixed, they warrant further study in phase 3 trials.
Bristol Myers and J&J plan to start a Phase 3 program by the end of the year that includes studies in atrial fibrillation, acute coronary syndrome and secondary stroke prevention. Bayer started two Phase 3 trials as well.
Shares of both sank in Monday trading, however. Bristol Myers shares fell by nearly 6% following the news. Bayer shares were down about 4%.