An investigational drug may make exercise and daily activities easier for patients with obstructive hypertrophic cardiomyopathy (HCM), according to a late-stage, placebo-controlled study recently published in The New England Journal of Medicine.

Maron MS, Masri A, Nassif ME, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. N Engl J Med. Published online May 13, 2024.

The study showed that people with the condition used more oxygen while exercising after taking aficamten.

 “By having more oxygen available during exercise, patients with obstructive [HCM] can more easily walk, perform household chores, and do other everyday tasks,” said study author Ahmad Masri, MD, in a press release.

Oregon Health & Science University. New drug makes exercise, everyday tasks easier for people with common heart condition [press release]. May 13, 2024.

“Our latest clinical trial results suggest aficamten is a promising treatment for HCM.”

Common heart condition 

In obstructive HCM, the thickened heart muscle obstructs the outflow of blood from the left ventricle, increasing cardiac pressure.

American Heart Association. Hypertrophic Cardiomyopathy (HCM). May 13, 2022.

People with HCM may be asymptomatic, but the condition can present as chest pain or breathlessness, particularly with physical exertion. It can also cause fatigue, dizziness, lightheadedness, syncope, arrhythmias, or edema in the legs or abdomen, leading people with HCM to limit their activity. As a chronic disease that progresses with time, HCM can lead to atrial fibrillation, heart failure, or, rarely, sudden cardiac arrest.

Current treatment guidelines for obstructive HCM includes surgery to remove excess heart muscle or the use of mavacamten (Camzyos) capsules.

Oregon Health & Science University. New drug makes exercise, everyday tasks easier for people with common heart condition [press release]. May 13, 2024.

Phase 3 trial

 Aficamten is an oral selective cardiac myosin inhibitor that lessens excessive cardiac contraction, reducing pressure in the left ventricular outflow tract. The study evaluated its efficacy and safety in 282 adults (mean age, 59.1 years; 59.2% men) with symptomatic obstructive HCM. At baseline, their mean resting left ventricular outflow tract gradient was 55.1 mm Hg and their left ventricular ejection fraction was 74.8%.

Maron MS, Masri A, Nassif ME, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. N Engl J Med. Published online May 13, 2024.

The participants were randomly assigned to receive aficamten or placebo for 24 weeks. They started on a dose of 5 mg; the maximum dose permitted was 20 mg. Adjustments to the dose were based on echocardiography results.

The primary endpoint was the peak oxygen uptake change from baseline to week 24, as assessed by cardiopulmonary exercise testing. At week 24, the mean change in the peak oxygen uptake was 1.8 vs 0.0 mL per kg per minute for aficamten vs placebo (least-squares mean between-group difference, 1.7 mL/kg/min; 95% CI, 1.0 to 2.4; P<0.001).

The researchers also assessed the following secondary endpoints at 12 and 24 weeks: change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS); improvement in the NYHA functional class; change in the pressure gradient after the Valsalva maneuver; and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver. The duration of eligibility for septal reduction therapy and change in the total workload, as assessed by cardiopulmonary exercise testing, were also measured at week 24.

“This is an exciting time for treating HCM,” Dr. 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.”