Illustration of human artery that is blocked by plaque buildup of cholesterol
SBIR Success Stories
New Drug Has Potential to Slow Development of Coronary Heart Disease

Through support from the Small Business Innovation Research (SBIR) program of the National Heart, Lung, and Blood Institute (NHLBI), AlphaCore Pharma, a Michigan-based biotech company, initiated development of a novel drug that could potentially prevent or slow coronary heart disease (CHD) in certain people. The therapy has shown promising results and is advancing toward clinical trials. 

Illustration of human artery that is blocked by plaque buildup of cholesterol
Illustration of human artery that is blocked by plaque buildup of cholesterol

Taking Aim at ‘Bad’ Cholesterol

CHD, the most common type of heart disease, is responsible for nearly 400,000 deaths in the United States annually. CHD is caused by a buildup of plaque inside arteries, a condition known as atherosclerosis, and can result in a heart attack or stroke.

The AlphaCore drug, known as rhLCAT, is based on the naturally occurring enzyme lecithin cholesterol acyltransferase (LCAT), which works by enhancing the ability of high-density lipoprotein, or HDL, particles to remove excess harmful cholesterol from the arteries. Cholesterol that is bound to HDL is termed “HDL cholesterol” and is commonly called “good” cholesterol.

“Accumulation of cholesterol in plaques is fed by low-density lipoprotein cholesterol, also known as ‘bad’ cholesterol,” said AlphaCore’s Reyn Homan, PhD, who along with Brian R. Krause, PhD, and Bruce Auerbach, MS, developed rhLCAT for clinical use. “As more cholesterol accumulates in the coronary arteries, the plaques grow, restricting blood flow and weakening the artery wall to a point where it can rupture, resulting in the formation of a clot that completely blocks flow. The consequence is a heart attack.”

Dr. Homan explained that although current therapies are improving patient outcomes, the prevalence of atherosclerosis and its health risks remain high. As a result, scientists began to focus on boosting the function of LCAT.

LCAT converts cholesterol into a form that is easily taken up by HDL particles. HDL then carries the cholesterol away from the artery walls to the liver and eventually out of the body, preventing plaque buildup.

Early NIH-Supported Research Paves the Road to a New Cholesterol Drug

In early research studies at the NHLBI, Alan Remaley, MD, PhD, showed that rabbits that overproduce LCAT were protected against diet-induced atherosclerosis, displaying increased levels of HDL-cholesterol and reduced plaques in their arteries. These results led Dr. Homan and his colleagues to theorize that rhLCAT could have a therapeutic benefit for people who have, or are at risk of, CHD. The team established AlphaCore Pharma in 2007 to explore the potential of rhLCAT as a treatment for this group.

With funding from the NHLBI SBIR program, the AlphaCore group initiated a proof-of-principle study of rhLCAT by first developing a cell line to produce the enzyme and then injecting the enzyme in mice to demonstrate HDL-cholesterol elevation. This preliminary study enabled AlphaCore to gain additional support from a variety of private-sector investors. Additional SBIR-funded studies confirmed the efficacy and safety of rhLCAT in animal models, which was needed to obtain clearance from the Food and Drug Administration to initiate clinical studies. All of the animal studies produced favorable results.

Dr. Homan and his colleagues also obtained assistance from the NIH’s Bridging Interventional Development Gaps (BrIDGs) program, formerly known as NIH Rapid Access to Interventional Development. Additional support for the development of rhLCAT was provided by NHLBI’s Science Moving Towards Research Translation and Therapy, or SMARTT, program, which facilitates the transition of promising new therapies into clinical testing.

In 2013, less than six years after AlphaCore’s founding, the company was acquired by AstraZeneca on the strength of rhLCAT’s potential as a treatment for CHD. “It was the SBIR program that got us off the ground and helped us move so quickly,” acknowledged Dr. Homan. “Hopefully, that accelerated development will also translate into accelerated availability of the drug to patients.”

In early clinical AlphaCore-funded studies, rhLCAT has shown promising results and AstraZeneca is continuing its development.

Summary

NHLBI’s SBIR program was instrumental in helping AlphaCore to advance the development of rhLCAT as a cholesterol-lowering drug for the treatment of coronary heart disease.  The drug has the potential to improve health and survival for thousands of people suffering from CHD.  

More about the NHLBI SBIR and STTR programs

The NHLBI Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs support research and development on the next generation of commercially promising technologies and products to prevent, diagnose, and treat heart, lung, blood, and sleep-related diseases and disorders.  For more information on NHLBI’s Small Business program, visit http://www.nhlbi.nih.gov/research/funding/sbir/about-program

Disclaimer

Reference to any specific commercial products, process, service, manufacturer, and/or company does not constitute an endorsement or recommendation by the National Heart, Lung, and Blood Institute (NHLBI), the NHLBI’s Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, or any other portion of the U.S. Government.