# Aficamten bij obstructieve hypertrofische cardiomyopathie: fase 2 resultaten

*geplaatst 2023-01-03 · Hartfalen · Journal of the American College of Cardiology · doi 10.1016/j.jacc.2022.10.020 · https://hartvaat.nl/2023/01/03/aficamten-bij-obstructieve-hypertrofische-cardiomyopathie-fase-2-resultaten/*

Fase 2 studie van aficamten, een volgende-generatie cardiale myosineremmer, toonde dosisafhankelijke verlaging van de LVOT-gradiënt en verbetering van symptomen bij obstructieve HCM. Aficamten is een veelbelovend alternatief voor mavacamten met een breder therapeutisch venster.

## English: Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy.

This phase 2 study of aficamten, a next-generation cardiac myosin inhibitor, showed dose-dependent reduction of the LVOT gradient and symptom improvement in patients with obstructive hypertrophic cardiomyopathy. The results advanced aficamten toward phase 3 development as an alternative to mavacamten.

## Abstract (original, from the publication)

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients. OBJECTIVES: This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM. METHODS: Patients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout. RESULTS: From baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: -40 ± 27 mm Hg, and -43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (-36 ± 27 mm Hg and -53 ± 44 mm Hg, P = 0.001 and <0.0001 vs placebo, respectively). There were modest reductions in EF (-6% ± 7.5% and -12% ± 5.9%, P = 0.007 and P < 0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro-B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms. CONCLUSIONS: Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM.

Auteurs: Martin S Maron, Ahmad Masri, Lubna Choudhury, Iacopo Olivotto, Sara Saberi, Andrew Wang, Pablo Garcia-Pavia, Neal K Lakdawala, Sherif F Nagueh, Florian Rader, Albree Tower-Rader, Aslan T Turer, Caroline Coats, Michael A Fifer, Anjali Owens, Scott D Solomon, Hugh Watkins, Roberto Barriales-Villa, Christopher M Kramer, Timothy C Wong, Sharon L Paige, Stephen B Heitner, Stuart Kupfer, Fady I Malik, Lisa Meng, Amy Wohltman, Theodore Abraham

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Bron: Journal of the American College of Cardiology, https://doi.org/10.1016/j.jacc.2022.10.020. Bijgewerkt 2026-07-03T18:38:59Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.