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

Tower-Rader, A, Masri, A ORCID: 0000-0002-6390-6526, Nassif, ME, Abraham, TP ORCID: 0000-0003-3411-1334, Barriales-Villa, R ORCID: 0000-0002-6721-3487, Choudhury, L, Cooper, RM ORCID: 0000-0001-7482-828X, Elliott, PM, Maron, MS, Olivotto, I, Oreziak, A, Owens, AT ORCID: 0000-0002-9669-8495, Solomon, SD, Heitner, SB, Jacoby, DL, Kupfer, S ORCID: 0000-0002-5469-1287, Liu, X, Malik, FI, Melloni, C, Simkins, TJ et al (2026) Aficamten in symptomatic obstructive hypertrophic cardiomyopathy: the FOREST-HCM long-term study. European Heart Journal. pp. 1-12. ISSN 0195-668X

Preview

Text Aficamten in symptomatic obstructive hypertrophic cardiomyopathy- the FOREST-HCM long-term study..pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

BACKGROUND AND AIMS: Aficamten is a next-in-class, oral selective cardiac myosin inhibitor that ameliorates hypercontractility in hypertrophic cardiomyopathy (HCM). This study assessed the safety and efficacy of extended aficamten treatment in symptomatic obstructive HCM (oHCM).

METHODS: Patients completing a parent aficamten study were eligible to enrol in FOREST-HCM (NCT04848506), an open-label study evaluating long-term aficamten treatment.

RESULTS: Patients with oHCM (N = 296; mean age ±SD 61 ± 12.3 years, 44.3% female) enrolled between May 2021 and August 2024. Cumulative exposure was 352 patient-years; median follow-up 51.6 (IQR 41.5, 70.8) weeks. At Weeks 12 and 96, aficamten reduced Valsalva left ventricular outflow tract gradient by 56 ± 43 and 62 ± 33 mmHg from baseline (both P < 0.0001), with minimal reduction in left ventricular ejection fraction (LVEF) (-3% ± 6% and -5% ± 5%); 69% and 93% of participants had at least one NYHA class improvement; Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score improved by 15 ± 16 and 16 ± 16 points. Treatment-emergent serious adverse events (TESAEs) occurred in 36 (12.2%) patients; no deaths, heart failure, or events considered related to aficamten were reported. One (0.3%) patient terminated therapy due to a TESAE (ischemic colitis). LVEF<50% occurred in 10 (3.4%) patients [exposure-adjusted incidence rate (EAIR): 2.9 per 100 patient-years] with 2 having non-serious mild/moderate dyspnoea. No treatment interruptions for LVEF<50%, and no events of LVEF<40% occurred. New-onset atrial fibrillation occurred in seven (2.4%) patients (EAIR 2.0 per 100 patient-years).

CONCLUSIONS: Extended aficamten treatment in patients with symptomatic oHCM yielded early and sustained hemodynamic and clinical responses with low incidences of new-onset atrial fibrillation and LVEF<50%.

Item Type:	Article
Uncontrolled Keywords:	Aficamten; Efficacy; Hypertrophic cardiomyopathy; Open-label extension; Safety; 32 Biomedical and Clinical Sciences; 3202 Clinical Sciences; Pediatric Research Initiative; Cardiovascular; Pediatric Cardiomyopathy; Rare Diseases; Clinical Trials and Supportive Activities; Heart Disease; Patient Safety; Clinical Research; 6.1 Pharmaceuticals; Cardiovascular; 1102 Cardiorespiratory Medicine and Haematology; 1103 Clinical Sciences; Cardiovascular System & Hematology; 3201 Cardiovascular medicine and haematology; 3202 Clinical sciences
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Divisions:	Sport and Exercise Sciences
Publisher:	Oxford University Press
Date of acceptance:	18 December 2025
Date of first compliant Open Access:	17 March 2026
Date Deposited:	17 Mar 2026 09:53
Last Modified:	17 Mar 2026 09:53
DOI or ID number:	10.1093/eurheartj/ehaf1085
URI:	https://researchonline.ljmu.ac.uk/id/eprint/28248

View Item