Independent, scheduled review finds Librexia ACS trial unlikely to meet primary efficacy endpoint, leading to decision to discontinue trial
Librexia AF and Librexia STROKE studies continue as planned, with data expected in 2026
Milvexian continues to have potential as a multi-billion-dollar asset that could redefine anticoagulant therapy for thrombotic diseases
Bristol Myers Squibb (NYSE:BMY) in collaboration with Johnson & Johnson today announced the decision to stop the Phase 3 Librexia ACS trial evaluating the efficacy and safety of milvexian when added to the standard of care (conventional antiplatelet therapy) for patients after a recent acute coronary syndrome (ACS) event. The decision to discontinue the trial follows a preplanned interim analysis by the Independent Data Monitoring Committee (IDMC), which determined the trial is unlikely to meet the primary efficacy endpoint.
No new safety concerns related to the investigational therapy were identified. The safety profile was consistent with previously reported studies of milvexian.
The Librexia clinical trial program includes two other Phase 3 trials, Librexia AF for patients with atrial fibrillation (AF) and Librexia STROKE for secondary stroke prevention (SSP). The IDMC recommended these trials continue as planned, with topline data expected in 2026.
"Together with Johnson & Johnson, we remain confident in the potential of milvexian to redefine anticoagulant therapy and provide patients and clinicians a new therapeutic option for reducing thrombosis risks without significantly increasing potential bleeding risks," said Roland Chen, MD, senior vice president, drug development, Immunology and Cardiovascular Medicines, Bristol Myers Squibb. "Our belief in both the SSP and AF studies remains high and is rooted in robust data from large Phase 2 clinical studies conducted in relevant patient populations and on different background treatment. The Librexia SSP and AF studies are distinct from Librexia ACS in several aspects, including patient populations, endpoints, type and duration of background therapy and disease pathology."
Study investigators will be updated, and the data will be shared with the scientific community at a future medical congress.
"Today's news confirms the complexity of treating ACS and the need to further advance knowledge of the disease," said Robert A. Harrington, MD, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, and Librexia program chair. "Given that milvexian did not lead to any new safety concerns in this trial, the inhibition of factor XIa continues to be a promising mechanism within the broader thrombotic treatment space that may lead to advances beyond the standard of care for thrombotic diseases."
Bristol Myers Squibb and Johnson & Johnson thank the patients, investigators and clinical trial sites who participated in the Librexia ACS trial.
About Acute Coronary Syndrome
Acute coronary syndrome (ACS) is an umbrella term for situations in which blood supplied to the heart muscle is suddenly reduced, usually due to a clot. ACS includes myocardial infarction (MI), also known as a heart attack, and unstable angina manifesting as sudden severe chest pain that typically occurs when a person is at rest or with minimal exertion. More than seven million people in the world are diagnosed with ACS every year. The risk of recurrent cardiovascular (CV) events, like MI, ischemic stroke and CV death remain high at more than 5% in the first year following the initial event. Despite advances in antithrombotic treatment, anticoagulation therapy is not frequently used in combination with antiplatelet therapy due to a potential risk of bleeding, leaving many ACS patients unprotected from thrombotic events.
About Milvexian
Milvexian is an investigational oral, highly selective factor XIa (FXIa) inhibitor, part of a new class of anticoagulants in development aimed at preventing harmful clotting that restricts blood flow (thrombosis) while preserving the normal clotting process (hemostasis). As a result, milvexian could potentially reduce major cardiovascular events due to harmful clotting without significantly increasing the risk of bleeding. It is currently being studied in the Phase 3 Librexia program, the most comprehensive FXIa clinical development program to date, for the prevention of major thrombotic conditions.
Milvexian is an investigational agent and has not been approved for use in any country for any indication.
About the Librexia Program
The Librexia program, which is being executed by Johnson & Johnson in collaboration with Bristol Myers Squibb, is the most comprehensive anti-FXIa clinical development program today, evaluating over 50,000 patients in three Phase 3 studies, including event reduction in acute coronary syndrome (Librexia ACS), stroke prevention in atrial fibrillation (Librexia AF) and stroke prevention after an acute ischemic stroke or high-risk transient ischemic attack (Librexia STROKE). Grounded in robust Phase 2 data, the Librexia program is designed to evaluate the benefit-risk profile for certain patient populations who should be receiving treatment but may not be due to the potential for increased bleeding risk. The program is developed and powered to potentially advance beyond the standard of care and help improve outcomes in a wide range of patients with certain thrombotic diseases.
About Librexia ACS
Librexia ACS (NCT05754957) was a randomized, double-blind, placebo-controlled, event-driven study to demonstrate the efficacy and safety of milvexian after a recent acute coronary syndrome (ACS).
Eligible patients for enrollment were adults at least 18 years of age within seven days of an ACS, who had undergone cardiac catheterization with percutaneous coronary intervention or were being managed conservatively with or without catheterization, and were receiving standard of care antiplatelet therapy. Additionally, patients must have had at least two risk-enhancing factors associated with an increase in the risk of recurrent ischemic events.
The primary endpoint was time to first occurrence of Major Adverse Cardiovascular Events (MACE, a composite of cardiovascular death, myocardial infarction and ischemic stroke) compared to placebo, when added to conventional antiplatelet therapy. Secondary endpoints included time to first occurrence of composite all-cause mortality (AMC), myocardial infarction and ischemic stroke; time to cardiovascular death; time to AMC.
About Librexia AF
Librexia AF (NCT05757869) is a randomized, double-blind, double-dummy, parallel group, active-controlled study to evaluate the efficacy and safety of milvexian versus apixaban in participants with atrial fibrillation (AF).
Eligible patients for enrollment are adults at least 18 years of age, medically stable, appropriate for chronic antithrombotic treatment and with AF eligible to receive anticoagulation. Additionally, patients must satisfy one or both of the following categories of risk factors (a or b): a) one or more of the following risk factors: i) age greater than or equal to 75 years, ii) history of any type of stroke including symptomatic stroke of any kind; b) two or more of the following risk factors: i) age between 65 and 74 years, ii) hypertension, iii) diabetes mellitus, iv) atherosclerotic vascular disease, v) heart failure.
The primary endpoint is the time to first occurrence of composite endpoint of stroke and non-central nervous system (CNS) systemic embolism. Secondary endpoints include time to first occurrence of: International Society of Thrombosis and Hemostasis (ISTH) major bleeding; composite of ISTH major and clinically non-major (CRNM) bleeding; composite endpoint of stroke, non-CNS systemic embolism and ISTH major bleeding; composite endpoint of CV death, myocardial infarction (MI), stroke and non-CNS systemic embolism; cardiovascular death; composite endpoint of all-cause death, MI, stroke and non-CNS systemic embolism; composite endpoint of CV death, MI, stroke, any unanticipated revascularization or amputation of ischemic limb and urgent hospitalization for vascular cause of ischemic nature, including deep vein thrombosis and pulmonary embolism.
About Librexia STROKE
Librexia STROKE (NCT05702034) is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study to demonstrate the efficacy and safety of milvexian in addition to single or dual antiplatelet therapy for stroke prevention after an acute ischemic stroke or high-risk transient ischemic attack.
Eligible patients for enrollment are adults at least 40 years of age with ischemic stroke, a neurological deficit attributable to an acute brain infarction and National Institute of Health stroke score scale (NIHSS) score less than or equal to seven and at least one of the following: persistent signs or symptoms of the ischemic event at the time of randomization, acute ischemic brain lesion determined by standard of care neuroimaging, underwent thrombolysis or thrombectomy or transient ischemic attack (acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete symptom resolution of the deficit and no brain infarction on neuroimaging). Participants are randomized as soon as possible after determining eligibility and within 48 hours of onset of event.
The primary endpoint is the time to first occurrence of ischemic stroke. Secondary endpoints include time to first occurrence of: any component of the composite of cardiovascular death (CVD), myocardial infarction (MI) or ischemic stroke; ischemic stroke in the first 90 days; any component of major adverse vascular event (composite of CVD, MI, ischemic stroke, major adverse limb events, symptomatic pulmonary embolism or deep vein thrombosis).
About the Bristol Myers Squibb-Johnson & Johnson Collaboration
Bristol Myers Squibb and Johnson & Johnson, two leaders in cardiovascular care, are determined to close the gap in unmet needs in thrombosis management by overcoming the limits of today's treatments. The collaboration to develop and commercialize milvexian aims to leverage the combined scientific expertise and world-class commercial capabilities of each company, to improve patient outcomes. The alliance is uniquely equipped to deliver on the promise of FXIa inhibitors and is working diligently to evaluate the safety and efficacy of treatment options for patients with thrombotic diseases.
About Bristol Myers Squibb: Transforming Patients' Lives Through Science
At Bristol Myers Squibb, our mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. We are pursuing bold science to define what's possible for the future of medicine and the patients we serve. For more information, visit us at BMS.com or follow us on LinkedIn, X, YouTube, Facebook and Instagram.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, the possibility of unfavorable results from further clinical trials involving milvexian and whether milvexian for the indications described in this release will be successfully developed and commercialized. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb's business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2024, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
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