People with hypertrophic cardiomyopathy were able to use significantly more oxygen while exercising after taking an investigational drug in an international clinical trial, according to a study published today in the New England Journal of Medicine. The finding was also presented at the European Society of Cardiology’s Heart Failure 2024 meeting in Lisbon, Portugal.
The randomised, double-blind Phase 3 trial has 282 participants and is evaluating the experimental drug aficamten, which was developed by Cytokinetics to treat the obstructive form of hypertrophic cardiomyopathy, or HCM.
“By having more oxygen available during exercise, patients with obstructive hypertrophic cardiomyopathy can more easily walk, perform household chores, and do other everyday tasks,” said cardiologist and paper co-author Ahmad Masri, MD, MS. Masri directs the Oregon Health & Science University Knight Cardiovascular Institute’s Hypertrophic Cardiomyopathy Center. “Our latest clinical trial results suggest aficamten is a promising treatment for HCM.”
HCM affects about 1 in 500 people and is one of the most common causes of sudden death for youth and otherwise healthy athletes. Often caused by inherited gene mutations, it thickens heart muscles and makes it difficult for the heart to work as it should. It causes shortness of breath and reduces people’s ability to exercise. The obstructive form of HCM reduces blood flow out of the heart.
About half of the trial’s participants randomised to aficamten. Scientists measured the participants’ oxygen levels while they used treadmills or bicycles. Those who took aficamten had a significant increase in their maximum oxygen use – 1.7mL/kg/min more than those in the control group taking placebo.
Having an increased peak oxygen uptake can improve a patient’s ability to be physically active, whereas reduced oxygen uptake can increase the risk of experiencing heart failure, needing a heart transplant, and dying.
A safer alternative
Non-drug treatment options for obstructive HCM include surgery to remove excess heart muscle. In 2022, the Food and Drug Administration also approved mavacamten as the first drug designed to target the underlying cause of obstructive HCM. However, mavacamten may increase the risk of heart failure and it interacts with several commonly used medications. As a result, patients who use mavacamten must also undergo intense monitoring.
During the past decade, OHSU has been involved in many research studies exploring new HCM treatment options. It has been a centre for several mavacamten studies and is participating in gene therapy research. The university is also currently involved in four other aficamten trials that are evaluating it as a potential treatment for various forms of HCM and in different types of patients, including children.
“This is an exciting time for treating HCM,” Masri said. “While we continue to offer traditional surgical and procedural therapies for HCM, we are now also able to offer patients other treatment options: therapies that were recently approved by the FDA and investigational therapies that are available by participating in clinical trials.”
