ESC Congress 2026: Aficamten shows promise for symptomatic nonobstructive hypertrophic cardiomyopathy

Clinical takeaway: Phase 3 trial in symptomatic nonobstructive hypertrophic cardiomyopathy showed that targeting cardiac myosin can improve exercise capacity, patient-reported health status, and functional class. If approved for nonobstructive disease, aficamten may provide the first disease-specific treatment option for these patients, with echocardiographic monitoring central to safe use.

Patients with symptomatic nonobstructive hypertrophic cardiomyopathy have limited treatment options and no approved therapy that directly addresses the underlying disease. Results presented at the European Society of Cardiology Congress 2026 and simultaneously published in The New England Journal of Medicine suggest the cardiac myosin inhibitor aficamten could help fill that gap.

The ACACIA-HCM trial included 517 adults who received aficamten or placebo for up to 72 weeks. Aficamten is already FDA approved for symptomatic obstructive hypertrophic cardiomyopathy, but its use in nonobstructive disease remains investigational.

At 36 weeks, peak oxygen uptake increased by 0.64 mL/kg/min with aficamten and was essentially unchanged with placebo, an adjusted difference of 0.67 mL/kg/min. Patient-reported health status improved by 11.4 points with aficamten and 8.4 points with placebo, a 3-point difference.

Aficamten also produced at least a one-class improvement in New York Heart Association functional class in 41.9% of patients versus 27.8% with placebo. The trial did not demonstrate a reduction in cardiovascular events.

Reversible reductions in left ventricular ejection fraction below 50% occurred in 10.5% of patients receiving aficamten versus 0.8% receiving placebo. Serious adverse events occurred in 20.2% and 14.7%, respectively. Heart-failure events with aficamten occurred during dose titration or before week 12 and generally responded to a short course of diuretic therapy.

Long-term safety is being evaluated in the FOREST-HCM extension study. Cytokinetics plans to submit a supplemental application to the FDA in the fourth quarter of 2026 seeking approval for adults with symptomatic nonobstructive hypertrophic cardiomyopathy.

“We look forward to applying this study’s groundbreaking scientific knowledge into clinical practice upon potential approval, addressing this area of HCM where patients do not have adequate treatment options,” said Ahmad Masri, MD, MS, ACACIA-HCM principal investigator.

Sources: Masri A, et al. (2026 Aug 28) N Engl J Med. Aficamten for symptomatic nonobstructive hypertrophic cardiomyopathy; Cytokinetics. (2026 Aug 28) Cytokinetics announces positive results from ACACIA-HCM presented at ESC Congress 2026