Key takeaways
There are currently no approved treatments for symptomatic non-obstructive hypertrophic cardiomyopathy (HCM).
The ACACIA-HCM trial compared the cardiac myosin inhibitor, aficamten, with placebo in patients with symptomatic non-obstructive HCM.
The trial met dual primary endpoints: aficamten significantly improved symptom burden and exercise capacity.
ACACIA-HCM is the first trial to document clinically meaningful improvements in this relatively common form of inherited heart disease.
Munich, Germany – 28 August 2026: Aficamten treatment was associated with significant improvements in symptom burden and exercise capacity in patients with symptomatic non-obstructive hypertrophic cardiomyopathy, according to results presented in a Hot Line session today at ESC Congress 20261 and published simultaneously in the New England Journal of Medicine.
Hypertrophic cardiomyopathy (HCM) is an inherited disease in which the heart muscle becomes abnormally thick. HCM can be obstructive, when the thickened muscle blocks blood flow, or non-obstructive, when blood flow is not blocked but heart function is still affected.
"Patients with non-obstructive HCM experience limiting symptoms that affect their daily lives. But despite this being a relatively common disorder, there are no effective therapies," explained Principal Investigator, Doctor Ahmad Masri from the Oregon Health & Science University, Portland, USA. "Building on our experience with the cardiac myosin inhibitor, aficamten, in obstructive HCM, we conducted the ACACIA-HCM trial to investigate its effects on symptom burden and exercise capacity in patients with non-obstructive HCM."
This was a double-blind, phase III trial conducted at 182 international sites. A total of 517 adults with symptomatic non-obstructive HCM were randomised (1:1) to aficamten or placebo for up to 72 weeks. The dose of aficamten was adjusted based on left ventricular ejection fraction (LVEF). The dual primary endpoints were change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and change in maximal exercise performance (pVO2) from baseline to week 36. The mean age of participants was 55 years, 54% were women and baseline LVEF was 68%.
Aficamten significantly improved the primary endpoint related to symptom burden. At 36 weeks, KCCQ-CSS improved by 11.4 in the aficamten group and 8.4 in the placebo group (p=0.02). Doctor Masri noted that improvements were seen "as early as 12 weeks and there was a pronounced return of symptoms after aficamten treatment was stopped."
Aficamten also significantly improved the primary endpoint related to maximal exercise performance at 36 weeks. pVO2 improved by 0.64 mL/kg/min in the aficamten group and was almost unchanged (−0.03 mL/kg/min) in the placebo group (p=0.003).
Significant improvements with aficamten were also seen in secondary endpoints including New York Heart Association functional class, submaximal exercise performance and NT-proBNP, a marker of heart strain.
Regarding safety, there was an increased incidence of patients having LVEF less than 50% with aficamten vs. placebo (10% vs. 1%) but this was managed with dose adjustment.
Concluding, Doctor Masri said: "Results from the ACACIA-HCM trial provide really positive news for patients with symptomatic non-obstructive HCM. For the first time, we have shown clinically meaningful improvements in symptoms and exercise capacity with a treatment that targets the cause of the disease."
