Aficamten Safe, Efficacious in nHCM, Improves Symptoms and Exercise Capacity

Patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM) who were treated with aficamten saw significant improvements in symptom burden and exercise capacity, according to full results from ACACIA-HCM.¹

These data were presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Ahmad Masri, MD, MS, cardiomyopathy section head at Oregon Health & Science University, director of the OHSU hypertrophic cardiomyopathy center and the OHSU Knight Cardiovascular Institute Cardiac Amyloidosis Program, and co-author of the study.¹

“Non-obstructive HCM represents a substantial proportion of patients with HCM who arguably have the highest unmet need right now, since they don’t have any therapies available or approved that can actually improve their symptoms and exercise capacity,” Masri told HCPLive in an exclusive interview.

ACACIA-HCM was a double-blind phase 3 trial, conducted across 182 sites internationally. Patients were eligible for inclusion if they were between 18 and 85 years of age with a body mass index <40 kg/m2. Additionally, patients were required to have a respiratory exchange ratio ≥1 at screening by cardiopulmonary exercise testing and predicted peak oxygen uptake ≤90% for age and sex. Patients with significant valvular heart disease, infiltrative, genetic, or storage disorder causing cardiac hypertrophy, or unrevascularized coronary artery stenosis of ≥70%, among other criteria, were excluded.²

A total of 517 patients were enrolled in the trial and randomly assigned in a 1:1 ratio to aficamten or placebo. Treatment continued for ≤72 weeks. Aficamten doses were adjusted based on LV ejection fraction (LVEF). The trial featured a dual primary endpoint of change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and in maximal exercise performance (pVO2) from baseline to week 36.¹

At 36 weeks, Masri and colleagues found that KCCQ-CSS had improved by 11.4 in the aficamten group compared to 8.4 in the placebo group (P = .02). These benefits were noted as early as 12 weeks, according to the team. pVO2 also improved by 0.64 mL/kg/min in the aficamten group while remaining almost fully unchanged in the placebo group (-.03 mL/kg/min) (P = .003).¹

Secondary endpoints, such as New York Heart Association functional class, submaximal exercise performance, and NT-proBNP, also saw improvements with aficamten treatment. The trial did display an increased incidence of patients with LVEF <50% with aficamten (10%) compared to placebo (1%), but this was managed through dose adjustment and no patients discontinued treatment.¹

Ultimately, Masri and colleagues concluded the definitive improvements provided by aficamten in this population, highlighting its clear efficacy in reducing symptoms for nHCM. In the interview, Masri expressed anticipation of results from the trial’s long-term extension, FOREST-HCM, which includes >80% of the patients from ACACIA-HCM following trial completion.¹

“What we are looking forward to is the long-term extension, FOREST-HCM, which will provide more data on the longer-term exposure to aficamten and what the results could look like for those patients,” Masri said. “We will also at some point report results from the echocardiographic outcomes as well as the cardiac MRI substudy related to that change in structure and function. So, stay tuned.”

Editors’ Note: Masri reports disclosures with Pfizer, Attralus, Lexicon, Ionis, Cytokinetics, BioMarin, and others.

References

1. Masri A. ACACIA-HCM: Aficamten for symptomatic nonobstructive hypertrophic cardiomyopathy. Presented at the European Society of Cardiology Congress 2026, Munich, Germany. August 28-31, 2026.

2. Cytokinetics. A Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM) (ACACIA-HCM). ClinicalTrials.gov Identifier: NCT06081894. Updated August 5, 2026. Accessed August 28, 2026. https://clinicaltrials.gov/study/NCT06081894