Aficamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: 48-Week Results From FOREST-HCM
- PMID: 40540987
- DOI: 10.1016/j.jchf.2025.03.040
Aficamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: 48-Week Results From FOREST-HCM
Abstract
Background: Long-term safety and efficacy data for aficamten in symptomatic obstructive hypertrophic cardiomyopathy are needed.
Objectives: This 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.
Methods: Obstructive 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.
Results: From 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.
Conclusions: Aficamten 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).
Keywords: aficamten; clinical trial; efficacy; hypertrophic cardiomyopathy; long-term outcomes; safety.
Copyright © 2025. Published by Elsevier Inc.
Conflict of interest statement
Funding Support and Author Disclosures This study was funded by Cytokinetics, Inc. Dr Saberi has received consulting fees from Bristol Myers Squibb and Cytokinetics. Dr Choudhury has received advisor fees from Cytokinetics, Inc. Dr Barriales-Villa has received consultant/advisor fees from MyoKardia/Bristol Myers Squibb, Pfizer, Sanofi, Alnaylam, and Cytokinetics, Inc. Dr Elliott has received consulting fees from Bristol Myers Squibb, Pfizer, and Cytokinetics, Inc; speaker fees from Pfizer; and an unrestricted grant from Sarepta. Dr Nassif has received research and grant support to institution from Cytokinetics, Inc and Bristol Myers Squibb. Dr Oreziak has received investigator fees from Cytokinetics, Inc and MyoKardia/Bristol Myers Squibb. Dr Owens has received consultant/advisor fees from Alexion, Bayer, BioMarin, Bristol Myers Squibb, Cytokinetics, Inc, Corvista, Edgewise, Imbria, Lexeo, Stealth, and Tenaya; and research grants from Bristol Myers Squibb. Dr Tower-Rader has received research grants from Bristol Myers Squibb and Cytokinetics, Inc. Dr Rader has received consultant fees/honoraria from Medtronic, Cytokinetics, Inc, Bristol Myers Squibb, Idorsia, AstraZeneca, and Recor. Dr Garcia-Pavia has received Speakers Bureau fees from Bristol Myers Squibb, Pfizer, BridgeBio, Ionis, AstraZeneca, NovoNordisk, Intellia, and Alnylam; consulting fees from Bristol Myers Squibb, Cytokinetics, Inc, Rocket Pharma, Lexeo Therapeutics, Pfizer, Bayer, BridgeBio, Daiichi-Sankyo, Neurimmune, Alnylam, AstraZeneca, Novo Nordisk, Attralus, Intellia, Idoven, General Electric, and Alexion; and research/educational support to his institution from Pfizer, BridgeBio, NovoNordisk, AstraZeneca, Intellia, and Alnylam. Dr Olivotto has received Speakers Bureau fees from Bristol Myers Squibb, Amicus, and Genzyme; consultant/advisor fees from Bristol Myers Squibb, Cytokinetics Inc, Sanofi Genzyme, Amicus, Bayer, Tenaya, Rocket Pharma, and Lexeo; and research grant funding from Bristol Myers Squibb, Cytokinetics Inc, Sanofi Genzyme, Amicus, Bayer, Menarini International, Chiesi, and Boston Scientific. Dr Coats has received consultant/advisor fees from Alnylam, Cytokinetics, and Roche Diagnostics; and speaker fees from Pfizer. Dr Fifer has received consulting fees from Bristol Myers Squibb, Cytokinetics, Inc, Edgewise Therapeutics, and Viz.ai; and has received research grants from Bristol Myers Squibb and Novartis. Dr Sherrid has received consultant fees/honoraria from Pfizer Inc; and has served as a consultant for Cytokinetics Inc, without payment. Dr Solomon has received consultant/advisor fees from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health; and research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Inc, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi-Pasteur, Theracos, and US2.AI. Dr Watkins has received consultant/advisor fees from Cytokinetics, Inc, BioMarin, and BridgeBio. Drs Heitner, Jacoby, Kupfer, Malik, Melloni, Meng, and Wei are employees of Cytokinetics Inc and hold stock in Cytokinetics Inc. Dr Maron has received consultant/advisor fees from Imbria, Edgewise, and Biomarin; and steering committee fees for SEQUOIA-HCM from Cytokinetics, Inc. Dr Masri has received research grants from Pfizer, Ionis, Attralus, and Cytokinetics, Inc; and consulting fees from Cytokinetics Inc, BMS, Eidos/BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Lexeo, Prothena, BioMarin, AstraZeneca, and Tenaya. Dr Abraham has reported that he has no relationships relevant to the contents of this paper to disclose.
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