February is American Heart Month. Implemented by the National Heart, Lung and Blood Institute, American Heart Month is designed to provide awareness of heart problems and to encourage everyone to adopt heart healthy behaviors, such as healthy diet, controlling blood pressure and cholesterol, and exercise.
Alexander (Sasha) Opotowsky, associate professor at Harvard Medical School and a cardiologist at Boston Children’s Hospital and Brigham and Women’s Hospital took time out to speak with BioSpace about advances in heart health, congenital heart disease (CHD), biopharma, and the Adult Congenital Heart Association (ACHA). He emphasizes that he has research relationships with several of the companies mentioned in this article.
In the U.S., cardiovascular disease, including stroke, is the underlying cause of death in about 836,546 people each year, according to the American Heart Association (AHA). That comes to approximately 2,300 Americans dying each day from cardiovascular disease. And about 92.1 million U.S. adults have some type of cardiovascular disease or the after-effects of stroke.
Congenital heart disease, on the other hand, refers to a problem with the heart’s structure and is present at birth. It is rarer than cardiovascular disease and is usually defined by a string of birth defects, such as atrial septal defect, Tetralogy of Fallot, ventricular septal defect and others.
The ACHA is a patient advocacy group. Opotowsky says, “Their mission is to advance the care and improve the treatment for this population. They do this through a broad range of initiatives to educate patients, advocate for beneficial policy changes, and outreach to healthcare providers to enhance understanding of this diverse and unique group of patients.”
It also works to bring together patients, family and providers. “While the stated aim,” Opotowsky says, “is generally for providers to educate patients, this has an enormous effect on providers. Through these initiatives, the ACHA has nurtured a wonderful, close connection between patients and caregivers.”
For example, the ACHA has worked on improving the quality and availability of ACHD clinical services around the country. One way they did this is by developing criteria for what is expected of an ACHD clinical center as well as a process of certification to identify the programs that meet those criteria. Opotowski adds, “A second (way) is by working with clinical leaders to establish ACHD as a separate Board-Certified sub-specialty within Cardiovascular Disease, requiring specific fellowship training and a Board examination. Of course, this requires medical centers and trainees to dedicate additional resources and time to further training. The ACHA has partnered with philanthropic donors, including within the pharmaceutical industry, to establish funding for such clinical fellowships.”
Cardiac care and interventions often fall under the category of medical device companies. Often this is related to specific aspects of adult congenital heart disease (ACHD). “The first effective treatment of severe congenital heart diseases involved cardiac surgery,” Opotowsky says, “and surgical technology including prosthetic valves and grafts have long been an area of ongoing development, with close collaboration between industry and academia. Perhaps the most prominent recent growth in industry-related development has been in catheter-based intervention and device therapy.”
One example of advances in this area is a recent story that Abbott’s Amplatzer Piccolo Occluder was approved by the U.S. Food and Drug Administration (FDA). The device is smaller than a pea and is used to treat patent ductus arteriosus (PDA). This is a life-threatening hole in the heart of premature infants and newborns. PDAs make up 10 percent of all congenital heart disease.
“This approval is a potentially life-saving advance for the very smallest premature infants that will help us treat these delicate babies who might otherwise not be able to survive,” stated Evan Zahn, director of the congenital heart program at Cedars-Sinai’s Smidt Heart Institute and principal investigator for Abbott’s study.
Last year in March, the FDA approved Abbott’s Masters HP 15mm device, the world’s smallest mechanical heart valve. This is used to treat infants and children with mitral or aortic valve problems. It was initially developed by St. Jude Medical before Abbott bought the company.
Opotowski mentions other device developments, saying, “Many of these devices initially developed for specific needs in congenital heart disease have later been modified to be used in much larger cohorts of patients with common heart issues and acquired heart disease. One example is devices for closure of atrial septal defects and their application to patients with a patent foramen ovale and cryptogenic stroke.”
He goes on to say, “Another is percutaneous valve technology, which was first explored for pulmonary valve replacement in a subset of patients with CHD. There is now an explosion in transcatheter aortic valve disease for acquired aortic stenosis.”
Work on the medicinal front isn’t quite as common. However, one notable area is in pulmonary arterial hypertension (PAH). PAH is a form of high blood pressure that affects arteries in the lungs. In January 2017, Johnson & Johnson acquired Switzerland-based Actelion for $30 billion largely to acquire its Tracleer for PAH. The company also has Opsumit and Uptravi for PAH.
Opotowski says, “PAH is a disease which many patients with CHD are predisposed to developing.”
Another company working for treatments for cardiac diseases is BioCardia, based in San Carlos, Calif. The company’s lead therapeutic candidate is the CardiAMP Cell Therapy System. This provides an autologous bone marrow-derived cell therapy for the treatment of heart failure after a heart attack and chronic myocardial ischemia. The company presented positive 12-month data for CardiAMP at the American Heart Association meeting in November 2018 in adults experiencing heart failure after a heart attack.
Its second candidate is the CardiALLO Cell Therapy System, an allogeneic culture “off the shelf” cell therapy derived from donor bone marrow cells that meet specific criteria. It has the potential to treat a variety of clinical indications including heart failure.
And, of course, there is significant work on drugs to decrease cholesterol. The two biggest advances have been a class of drugs known as PCSK9 inhibitors, such as Regeneron Pharmaceuticals and Sanofi’s Praluent and Amgen’s Repatha.
In September 2018, Amarin Corporation announced positive data from its REDUCE-IT clinical trial of 8,179 statin-treated adults with increased risk of cardiovascular problems for its drug Vascepa. Vascepa is derived from a purified component of fish oil called eicosapentaenoic acid (EPA), and has been approved for patients with triglyceride levels higher than 500 milligrams per deciliter, triple normal levels. In the trial, the drug showed a 25 percent relative risk reduction in major adverse cardiovascular events compared to placebo.
And those are just some of the areas that life science companies are working on for heart health. Apotowski also points out that significant work is being conducted into diagnostic tests for cardiovascular disease. “We have recently been investigating the use of circulating and other biomarkers of cardiovascular disease in ACHD. We have worked with industry partners including companies which make diagnostic products (e.g. Roche Diagnostics) and others interested in supporting the understanding of how these tests may help better guide therapy (e.g. Actelion).