Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results from SEQUOIA-HCM (JACC November 2024-1)-Article: Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results from SEQUOIA-HCM

Article: Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results from SEQUOIA-HCM

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The SEQUOIA-HCM trial investigated the impact of Aficamten, a cardiac myosin inhibitor, on patients with obstructive hypertrophic cardiomyopathy (oHCM). This Phase 3 clinical trial involved 282 participants who were randomly assigned either Aficamten (142) or a placebo (140) for 24 weeks to examine its efficacy across various clinical outcomes. The study focused on several key measures: complete hemodynamic response, symptom relief, enhanced exercise capacity, and reduction of cardiac biomarkers.<br /><br />Results indicated that Aficamten significantly outperformed the placebo across all metrics. Specifically, 68% of Aficamten patients experienced a complete hemodynamic response compared to 7% of placebo patients. Improvement in limiting symptoms was noted in 71% of the Aficamten group versus 42% in the placebo group. Enhanced exercise capacity was seen in 47% of individuals on Aficamten, compared to 24% on placebo. Additionally, 84% of the Aficamten group achieved a 50% reduction in N-terminal pro–B-type natriuretic peptide, a biomarker of cardiac stress, compared to just 8% in the placebo group.<br /><br />By the end of the treatment period, 97% of patients on Aficamten showed improvement in at least one clinical measure, whereas only 59% in the placebo group did. Moreover, 23% of those in the Aficamten group improved in all four outcome measures, compared to none in the placebo group. Aficamten also reduced the eligibility for septal reduction therapy in symptomatic patients with high outflow gradients.<br /><br />Overall, Aficamten demonstrated broad clinical efficacy, contributing to symptom relief, improved exercise capacity, and lower cardiac biomarkers in patients with oHCM, suggesting its potential as a significant therapeutic option in this patient population. These results highlight the promising role Aficamten could play in the management of obstructive hypertrophic cardiomyopathy, potentially offering an alternative to invasive therapies like septal reduction procedures.

Keywords

SEQUOIA-HCM trial

Aficamten

cardiac myosin inhibitor

obstructive hypertrophic cardiomyopathy

Phase 3 clinical trial

hemodynamic response

exercise capacity

cardiac biomarkers

N-terminal pro–B-type natriuretic peptide

septal reduction therapy