Aficamten in symptomatic obstructive hypertrophic cardiomyopathy: the FOREST-HCM long-term study

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy and often presents with obstructive symptoms.
• Cardiac myosin inhibitors offer a novel therapeutic approach by targeting the hypercontractility underlying HCM.
• Aficamten is an oral selective cardiac myosin inhibitor designed to treat symptomatic obstructive HCM (oHCM).

Purpose of the Study:

• To assess the safety and efficacy of extended treatment with aficamten in patients with symptomatic oHCM.
• To evaluate long-term hemodynamic and clinical outcomes in patients receiving aficamten.

Main Methods:

• The FOREST-HCM study (NCT04848506) was an open-label trial for patients who completed a prior aficamten study.
• 296 patients with oHCM were enrolled, with cumulative exposure reaching 352 patient-years.
• Safety and efficacy endpoints were assessed up to 96 weeks of follow-up.

Main Results:

• Aficamten significantly reduced the Valsalva left ventricular outflow tract gradient at Weeks 12 and 96 (P < 0.0001).
• Clinical improvements included NYHA class and Kansas City Cardiomyopathy Questionnaire scores, with minimal impact on left ventricular ejection fraction (LVEF).
• Treatment-emergent serious adverse events were low (12.2%), with no deaths or aficamten-related heart failure; LVEF<50% occurred in 3.4% of patients.

Conclusions:

• Extended aficamten treatment provides early and sustained hemodynamic and clinical benefits in symptomatic oHCM.
• The cardiac myosin inhibitor demonstrated a favorable safety profile, with low incidences of atrial fibrillation and reduced LVEF.
• Aficamten represents a promising therapeutic option for long-term management of obstructive hypertrophic cardiomyopathy.