Adolescent patients with obstructive hypertrophic cardiomyopathy who received the drug mavacamten experienced significant improvement in a key measure of blood flow obstruction compared to those given a placebo, according to results presented at the American College of Cardiology's Annual Scientific Session on Mar. 29.
The findings are important because they represent the first time mavacamten has been tested in patients under 18 years old. The study addresses a gap in treatment options for children and teenagers with this genetic heart disorder, which can lead to serious complications including heart failure and death.
"These results are very encouraging," said Joseph William Rossano, MD, chief of cardiology at Children's Hospital of Philadelphia and the study's lead author. "Patients feel better, and their hearts look better."
Hypertrophic cardiomyopathy is caused by thickening of the heart muscle that can block or reduce blood flow from the left ventricle into the aorta. While adults have several treatment options approved by regulators such as the U.S. Food and Drug Administration, therapies for children have often proven less effective or safe.
Mavacamten works by inhibiting myosin—a protein involved in muscle contraction—thereby reducing how forcefully the heart squeezes. "This medicine was specifically designed for HCM and treats the underlying pathophysiology. This is what we hope to do in health care—to get medicines that are targeted for the underlying problem," Rossano said.
The phase 3 trial enrolled 44 patients aged 12-17 across North America, Europe, and Australia who had severe symptoms despite standard therapy. Participants were randomly assigned either mavacamten or placebo daily for 28 weeks. Those receiving mavacamten showed an average drop of 48.5 mmHg in their Valsalva LVOT gradient—the primary endpoint—compared to just a 0.5 mmHg reduction among those on placebo.
Secondary measures such as resting LVOT gradient, wall thickness of the left ventricle, peak oxygen consumption, fatigue levels, and shortness of breath also improved more among those taking mavacamten than placebo recipients over this period.
Rossano said laboratory markers associated with heart damage decreased among those taking mavacamten but increased among those on placebo: "Beyond symptom relief, there's a signal that this may be favorably remodeling the heart, which could improve the natural history of the disease," he said. He added that starting therapy early could help prevent decades-long injury from ongoing obstruction but emphasized longer-term follow-up is needed.
No major safety concerns were observed during this trial; adverse event rates were similar between groups without significant changes seen in ejection fraction—a measure reflecting how well blood is pumped out by each heartbeat.
Researchers acknowledged limitations including small sample size, short duration (28 weeks), and limited diversity among participants; most were White adolescents aged between twelve and seventeen years old. Plans call for continued monitoring through at least week fifty as well as possible future studies involving younger children or different forms of hypertrophic cardiomyopathy.
