Key result
Aficamten reduces Valsalva peak LVOT gradients by ~53 mm Hg in oHCM.
Why the study?
Long-term safety and efficacy data for aficamten in symptomatic obstructive hypertrophic cardiomyopathy are needed.
Does aficamten improve LVOT gradients and symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy?
Does aficamten improve LVOT gradients and symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy?
Long-term aficamten treatment over 48 weeks provides durable relief of LVOT obstruction, improves symptoms, and induces favorable cardiac remodeling in patients with symptomatic obstructive hypertrophic cardiomyopathy.
Aficamten was associated with reduced LVOT gradients over 48 weeks in obstructive HCM; extends short-term observations but leaves open randomized confirmation of outcomes.
BackgroundLong-term safety and efficacy data for aficamten in symptomatic obstructive hypertrophic cardiomyopathy are needed. ObjectivesThis study aims to evaluate 48-week experience from the ongoing FOREST-HCM (A Follow-Up, Open-Label, Research Evaluation of Sustained Treatment With Aficamten [CK-3773274] in Hypertrophic Cardiomyopathy) study. MethodsObstructive hypertrophic cardiomyopathy participants in an aficamten study (REDWOOD-HCM [Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM; NCT04219826]; SEQUOIA-HCM [Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT05186818]) could enroll in this phase 2/3, open-label, extension study. Participants received aficamten 5 mg once daily titrated ≤20 mg based on site-read echocardiographic assessments of Valsalva left ventricular outflow tract gradient and left ventricular ejection fraction. ResultsFrom May 2021 to October 2023, 213 participants enrolled; 46 participants with 48 weeks of follow-up were evaluated (mean age: 59.7 years; female: n = 26 [56.5%]). There were rapid, substantial, and sustained reductions in mean resting (−40 ± 34 mm Hg) and Valsalva peak left ventricular outflow tract gradient (−53 ± 39 mm Hg) from baseline to week 48. A total of 82% experienced ≥1 NYHA functional class improvement; 31% experienced a 20-point improvement in Kansas City Cardiomyopathy Questionnaire–Clinical Summary score. There were substantial reductions (mean change) in maximum left ventricular wall thickness (−1.2 ± 1.6 mm; P < 0.0001), left atrial volume index (−3.5 ± 6.6 mL/m2; P = 0.0008), lateral E/e′ (−2.2 ± 6.1; P = 0.02), and cardiac biomarkers (P ≤ 0.0031). Aficamten was well tolerated with 2 (4.3%) asymptomatic and transient instances of left ventricular ejection fraction <50% (range: 47%-49%), neither resulting in drug discontinuation, and no new-onset atrial fibrillation. ConclusionsAficamten treatment over 48 weeks was well tolerated and associated with substantial and durable relief of obstruction and symptom burden, lower cardiac biomarker levels, and cardiac phenotypic changes, which may indicate favorable cardiac remodeling. (A Follow-Up, Open-Label, Research Evaluation of Sustained Treatment With Aficamten [CK-3773274] in Hypertrophic Cardiomyopathy [FOREST-HCM]; NCT04848506)
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Saberi et al. (2025) studied Symptomatic obstructive hypertrophic cardiomyopathy (n=213). Aficamten was evaluated on Mean resting and Valsalva peak left ventricular outflow tract gradient. Aficamten treatment over 48 weeks reduced mean resting (-40 mm Hg) and Valsalva peak left ventricular outflow tract gradient (-53 mm Hg) in patients with obstructive hypertrophic cardiomyopathy.
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