Aficamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: 48-Week Results From FOREST-HCM.

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Long-term safety and efficacy data for aficamten in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) are needed.
• Aficamten is an investigational cardiac myosin inhibitor.

Purpose of the Study:

• To evaluate the 48-week safety and efficacy of aficamten in patients with oHCM.
• To assess the impact of aficamten on left ventricular outflow tract (LVOT) gradients, functional status, and cardiac structure.

Main Methods:

• This is a phase 2/3, open-label, extension study (FOREST-HCM) for participants from prior aficamten trials (REDWOOD-HCM, SEQUOIA-HCM).
• Participants received aficamten titrated up to 20 mg daily, with dose adjustments based on LVOT gradient and LVEF.
• Echocardiographic and clinical assessments were performed throughout the 48-week study period.

Main Results:

• 46 participants completed 48 weeks of follow-up.
• Significant and sustained reductions in resting and Valsalva LVOT gradients were observed.
• 82% of participants improved at least one NYHA functional class, and 31% showed a 20-point improvement in the KCCQ-CSS.
• Reductions in LV wall thickness, left atrial volume, and cardiac biomarkers were noted.
• Aficamten was well-tolerated, with transient, asymptomatic instances of LVEF <50% in 4.3% of participants, not leading to discontinuation.

Conclusions:

• Aficamten treatment for 48 weeks is well-tolerated in patients with oHCM.
• The treatment provides substantial and durable relief of obstruction and symptom burden.
• Aficamten may promote favorable cardiac remodeling, evidenced by reduced cardiac biomarkers and structural changes.