Librexia ACS Trial Ends Early as Efficacy Endpoint Not Met, BMS and J&J Announce

Bristol Myers Squibb (NYSE: BMY) in collaboration with Johnson & Johnson has announced the discontinuation of the Phase 3 Librexia ACS trial evaluating Milvexian, an investigational oral factor XIa inhibitor. The trial tested the efficacy and safety of Milvexian added to the standard of care, which includes conventional antiplatelet therapy, for patients who recently experienced an acute coronary syndrome (ACS) event.

Reason for Discontinuation

The decision to stop the Librexia ACS trial followed a preplanned interim analysis performed by an Independent Data Monitoring Committee (IDMC). The committee determined that the study was unlikely to meet its primary efficacy endpoint, specifically the reduction of major adverse cardiovascular events (MACE) such as heart attack, stroke, or cardiovascular death, compared to standard treatment alone. Despite the lack of demonstrated efficacy in this trial population, no new safety concerns were identified. The safety profile of milvexian remained consistent with findings from earlier phase studies.

Trial Context and Design

The Librexia ACS trial (NCT05754957) was designed to enroll approximately 16,000 patients aged 18 years or older who had an ACS event within the past 7 days. These patients were treated with conventional antiplatelet therapies (such as aspirin or P2Y12 inhibitors like Brilinta or Plavix) alongside Milvexian or placebo. The trial aimed to assess whether Milvexian could reduce thrombotic events without significantly increasing bleeding risk.

ACS remains a critical global health challenge, with over 7 million new cases each year and a recurrent cardiovascular event risk exceeding 5% within the first year post-ACS. Combining anticoagulant therapy with antiplatelet agents is complex due to bleeding risk concerns, and Milvexian was hypothesized as a next-generation anticoagulant that might offer an improved safety-efficacy balance through selective factor XIa inhibition.

Ongoing Milvexian Phase 3 Program

The Librexia clinical program includes two other Phase 3 trials currently ongoing and unaffected by the ACS trial’s halt:

Librexia AF (NCT05757869): Evaluating Milvexian versus apixaban in patients with atrial fibrillation to prevent stroke and systemic embolism. This trial has the largest market potential and uses a higher Milvexian dose.

Librexia STROKE (NCT05702034): Assessing Milvexian added to antiplatelet therapy for secondary prevention in patients with recent ischemic stroke or high-risk transient ischemic attack.

Both are expected to report topline data in 2026. Bristol Myers Squibb and Johnson & Johnson remain optimistic about milvexian’s potential to redefine anticoagulant therapy and provide safer, effective treatment options in these indications.

Dr. Roland Chen, senior vice president of drug development at Bristol Myers Squibb, underscored confidence in the ongoing AF and SSP trials, emphasizing key differences between these and the ACS study, including patient populations, endpoints, and background therapies.

Dr. Robert A. Harrington, dean of Weill Cornell Medicine and Librexia program chair, highlighted the complexity of treating ACS but expressed continued belief in factor XIa inhibition as a promising mechanism within thrombosis treatment, noting no new safety issues in the discontinued trial.