70 years and counting: How Bristol Myers Squibb continues to lead innovation for patients with cardiovascular disease

Over the last 100 years the death rate from cardiovascular disease (CVD) has been cut in half, in part due to scientific discoveries including the powerful link between nutrition and exercise and heart health, interventions rapidly addressing coronary blood flow and the development of drugs for managing blood pressure, cholesterol levels, blood sugar/diabetes and anticoagulation. Yet, with CVD persisting as the leading cause of death worldwide, it’s clear that many challenges remain unsolved.

Bristol Myers Squibb has been at the forefront of advancing CVD therapies for decades. The development of angiotensin converting enzyme (ACE) inhibitors, cholesterol lowering agents, anticoagulants, antiplatelets, cardiac myosin inhibitors and other therapies have transformed heart health care and opened the door to treatment for millions of people worldwide. This expertise, combined with a strategic research approach, is being leveraged today to develop new, meaningful therapies across diseases with a high unmet need.

Building on industry-leading work

A precision research approach rooted in causal human biology guides the discovery of new therapeutic options in CVD. This approach allows researchers to think differently about therapeutic approaches within disease subsets as well as the target identification process. For instance, while many traditional cardiovascular medications indirectly affect how the heart functions, Bristol Myers Squibb takes a different approach by focusing on mechanisms that act directly on the heart muscle. As part of that focus, pioneering work in cardiac myosin inhibition redefined the treatment landscape for a form of hypertrophic cardiomyopathy (HCM):

• In patients with HCM, it is harder for the heart to relax normally and fill with blood, which reduces the amount of blood the left ventricle can hold and send to the body with each heartbeat. The thickened heart muscle also tends to pump with too much force, increasing the heart muscle workload, causing the heart to use too much energy with every beat. 
• Cardiac myosin inhibition may help improve the ability of the heart to relax, thus targeting the underlying cause of HCM.  

This knowledge is now being extended into other CVDs with a high unmet need, including for patients with heart failure with preserved ejection fraction (HFpEF):

• In patients with HFpEF, the heart muscle is unable to properly relax leading to limitations in physical activity and shortness of breath.
• A recent proof of concept Phase 2a clinical trial conducted by Bristol Myers Squibb showed that direct modulation of the heart muscle with a cardiac myosin inhibitor may help improve relaxation, and, in turn, reduce shortness of breath and other symptoms.

Our historical expertise and industry-leading work in thrombosis also exemplifies how we are accelerating the development of new medicines based on a strong understanding of causal human biology.

• Factor XIa (FXIa) inhibition was developed based on the biology of patients with hemophilia C who are naturally FXI-deficient.
• It was observed that these individuals had a lower risk of blood clots and stroke, and that spontaneous bleeding was uncommon.
• These observations, along with genetic and epidemiology data and preclinical models, supported the exploration of FXIa inhibition for the prevention and treatment of major thrombotic conditions.
• We are working to deliver on the promise of FXIa inhibitors through the Bristol Myers Squibb-Johnson & Johnson Collaboration.

Helping patients with CVD live and feel better

Bristol Myers Squibb is dedicated to discovering and developing next generation CVD therapies that not only improve clinical outcomes but also patients’ quality of life. Our researchers select clinical trial endpoints that capture how patients feel and can physically function on a day-to-day basis in addition to measuring key cardiovascular outcomes, such as hospitalizations or death due to cardiovascular disease. This patient-centric focus continues even after the primary randomized clinical trials are complete through collection of long-term extension and real-world data. This information provides ongoing insights on durability of safety and tolerability and how medicines perform over longer periods of time and in everyday settings, helping ensure the lives of patients living with CVD are improved.

With this commitment to helping patients live and feel better, a scientific discovery engine rooted in causal human biology and a precision medicine approach to research, Bristol Myers Squibb remains committed to pioneering life-changing cardiovascular therapies. We are motivated by the power of science and the opportunity to address some of the most complex diseases of our time. Our success in treating CVD to date combined with our legacy of pursuing bold science gives us confidence that we will continue to rise to the challenge.