This new drug makes exercise and everyday activity easier
Key Takeaways
Aficamten is a promising treatment for patients with obstructive hypertrophic cardiomyopathy (HCM).
A phase 3 study showed that people with the condition used more oxygen while exercising when taking aficamten vs placebo.
Using aficamten may make exercise and everyday activity easier for those with obstructive HCM.
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.[] 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.[] “Our latest clinical trial results suggest aficamten is a promising treatment for HCM.”
Common heart condition
HCM is the most common genetic heart disease, affecting approximately 1 in 500 people. It is primarily diagnosed in middle age, with obstructive HCM more common than non-obstructive HCM.
In obstructive HCM, the thickened heart muscle obstructs the outflow of blood from the left ventricle, increasing cardiac pressure.[]
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.[]
Camzyos received approval in 2022 from the US FDA to treat adults with symptomatic New York Heart Association (NYHA) class II–III obstructive HCM to improve exercise capacity and symptoms.[] However, patients who use mavacamten must be closely monitored, as the drug interacts with several commonly used medications.
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%.[]
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.
All the secondary endpoints improved with aficamten when compared with placebo. The incidence of adverse events was similar between aficamten and placebo.
“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.”
What this means for you
A late-stage, placebo-controlled study showed that people with obstructive HCM used more oxygen while exercising after taking aficamten. Treatment with the drug may make exercise and everyday activity easier for those with the condition.