J&J-Bristol Myers Milvexian Misses Phase 3 LIBREXIA ACS Endpoint in Full ESC Readout

Johnson & Johnson and Bristol Myers Squibb’s milvexian failed to reduce major cardiovascular events in the Phase 3 LIBREXIA ACS trial, according to the full results presented Saturday at ESC Congress 2026. The readout puts numbers around an efficacy failure that the companies had already signaled when they stopped the study for futility in November 2025.

After a median follow-up of 10 months, cardiovascular death, myocardial infarction or ischemic stroke occurred in 5.4% of patients assigned to milvexian and 5.1% of those receiving placebo. The hazard ratio was 1.05, with a 95% confidence interval of 0.91 to 1.21 and a p-value of 0.50, leaving no evidence that the 25 mg twice-daily regimen improved the trial’s primary efficacy endpoint.

The European Society of Cardiology’s full LIBREXIA ACS readout also showed no difference in the principal safety endpoint of intracranial or fatal bleeding. That endpoint occurred in 0.3% of patients in each group, with a hazard ratio of 1.04 and a 95% confidence interval of 0.58 to 1.87.

Full results confirm the efficacy miss

LIBREXIA ACS randomized 14,194 patients at 893 sites in 44 countries to oral milvexian 25 mg twice daily or matched placebo. Participants had experienced an acute coronary syndrome within seven days and had either undergone cardiac catheterization with percutaneous coronary intervention or were being managed conservatively. They also had to carry at least two factors associated with a higher risk of recurrent ischemic events, and all received antiplatelet therapy selected by the investigator.

The neutral result was not limited to the primary composite. ESC reported no difference between milvexian and placebo in the individual components of cardiovascular death, myocardial infarction and ischemic stroke, and no improvement in major secondary efficacy endpoints including all-cause mortality. In other words, the trial did not reveal an efficacy signal elsewhere that could offset the missed primary endpoint.

Milvexian did have the expected pharmacodynamic effect. Patients taking the drug showed prolonged activated partial thromboplastin time, which the investigators said indicated anticoagulant activity at the tested dose. That finding makes the result more informative than a simple failure to demonstrate drug exposure, but it does not establish why inhibiting factor XIa failed to reduce events in this post-ACS setting.

The safety data are more nuanced than the efficacy result. Intracranial or fatal bleeding was not increased, which is relevant because the development thesis for factor XIa inhibitors has centered on reducing thrombosis while avoiding some of the bleeding burden associated with conventional anticoagulation. LIBREXIA ACS did not demonstrate the hoped-for reduction in ischemic events, however, so the favorable comparison on that narrow safety endpoint could not rescue the study’s benefit-risk proposition for this indication.

The trial had already been stopped for futility

The endpoint miss itself was not a surprise by the time the ESC numbers arrived. On November 14, 2025, Bristol Myers Squibb and Johnson & Johnson announced that they would stop LIBREXIA ACS after a preplanned interim review by the independent data monitoring committee concluded that the trial was unlikely to meet its primary efficacy endpoint. At that time, the companies said no new safety concerns had been identified and that the other two Phase 3 LIBREXIA studies would continue.

ClinicalTrials.gov now lists the ACS study as completed, with an actual primary completion and study completion date of February 6, 2026 and actual enrollment of 14,194 patients. The August 29 ESC presentation is therefore important because it provides the full numerical outcome rather than simply repeating the earlier futility decision. Investors already knew the ACS program had failed to clear its planned efficacy bar; the new information shows the size and direction of the difference between milvexian and placebo and confirms that the formal analysis did not overturn the interim conclusion.

The setting was always a demanding test for an additional antithrombotic drug. Patients after an acute coronary syndrome remain at risk of recurrent ischemic events even after modern interventions and antiplatelet therapy, but adding anticoagulation can raise bleeding risk. Factor XIa inhibition has attracted attention because factor XI participates in thrombus formation while appearing less central to normal hemostasis than some established anticoagulation targets. LIBREXIA ACS tested whether that mechanism could add protection on top of standard post-ACS therapy without creating an unacceptable bleeding penalty.

Milvexian’s broader Phase 3 program continues

Johnson & Johnson and Bristol Myers Squibb are developing milvexian across three major thrombotic indications. In 2023, Johnson & Johnson said the FDA had granted Fast Track designation for the acute coronary syndrome, atrial fibrillation and secondary stroke-prevention programs. The companies described the combined LIBREXIA program as involving nearly 50,000 patients, although milvexian remains investigational and is not approved for any indication.

The two remaining Phase 3 studies address different clinical questions from ACS. LIBREXIA AF compares milvexian with apixaban in patients with atrial fibrillation and was listed by ClinicalTrials.gov in July as active but not recruiting, with 20,284 participants and an estimated primary completion date of October 31, 2026. LIBREXIA STROKE is evaluating milvexian against placebo on top of antiplatelet therapy after acute ischemic stroke or high-risk transient ischemic attack; Johnson & Johnson’s trial registry shows enrollment complete and a study end date in December 2026.

Those distinctions matter because the ACS failure does not automatically determine the outcome of the atrial-fibrillation or stroke studies. The patient populations, background therapies, comparators and efficacy endpoints differ, and the ESC investigators specifically cautioned that the remaining trials test milvexian in clinically distinct settings. The ACS result nevertheless removes one large potential indication from the development case unless future analysis produces a materially different regulatory path.

Bristol Myers Squibb had described milvexian as a potential multi-billion-dollar asset when the ACS study was halted in 2025. With the full ACS data now confirming no efficacy benefit, the commercial breadth of that thesis depends more heavily on the two remaining Phase 3 programs. The next concrete milestones are the planned completion of LIBREXIA AF later in 2026 and LIBREXIA STROKE afterward, though completion dates do not necessarily indicate when topline results will be released.