Coats CJ, Maron MS, Abraham TP, Olivotto I, Lee MMY, Arad M, Cardim N, Ma CS, Choudhury L, Düngen HD, Garcia-Pavia P, Hagège AA, Lewis GD, Michels M, Oreziak A, Owens AT, Tfelt-Hansen J, Veselka J, Watkins HC, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Meng L, Wohltman A, and Masri A
Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). This large, phase 3 trial is now fully enrolled (N = 282). Baseline characteristics reflect an ethnically diverse population with characteristics typical of patients encountered clinically with substantial functional and symptom burden. The study will assess the effect of aficamten vs placebo, in addition to standard-of-care medications, on functional capacity and symptoms over 24 weeks. Future clinical trials could model the approach in SEQUOIA-HCM to evaluate the effect of potential therapies on the burden of oHCM. (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM [SEQUOIA-HCM]; NCT05186818)., Competing Interests: Funding Support and Author Disclosures The SEQUOIA-HCM trial is funded by Cytokinetics, Incorporated. Representatives of Cytokinetics have been involved in the design and conduct of the study reported in this manuscript. Dr Coats has received speaker fees from Alnylam and Roche, and advisory fees from Cytokinetics. Dr Maron has received consultant/advisor fees from Imbria and Takeda, and Steering Committee fees for SEQUOIA-HCM from Cytokinetics, Incorporated. Dr Olivotto has received Speakers Bureau fees from Boston Scientific, Amicus, and Novartis; consultant/advisor fees from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Bayer, Tenaya, and Rocket Pharma; and research grant funding from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Bayer, Menarini International, and Boston Scientific. Dr Lee has received research grants to his institution from AstraZeneca and Boehringer Ingelheim, and Clinical Endpoint Committee fees from Bayer. Dr Arad has received consultant and lecture fees from Bristol Myers Squibb. Dr Cardim is on the advisory boards for Bristol Myers Squibb and Cytokinetics. Dr Düngen has received grants from Novartis, CSL Behring, and Cytokinetics. Dr Garcia-Pavia has received Speakers Bureau fees from Pfizer, AstraZeneca, NovoNordisk, Bristol Myers Squibb, BridgeBio, Ionis, and Alnylam; consultant/advisor fees from Pfizer, Alnylam, MyoKardia/Bristol Myers Squibb, Cytokinetics, Neurimmune, BridgeBio, Attralus, Intellia, Rocket Pharma, Lexeo Therapeutics, and AstraZeneca; and research/educational grants to his institution from Pfizer, BridgeBio, NovoNordisk, AstraZeneca, and Alnylam. Dr Hagège has received consultant/advisor fees from Alnylam, Amicus Therapeutics, Bayer, MyoKardia/Bristol Myers Squibb, Pfizer, and Sanofi Genzyme; and Steering Committee fees for SEQUOIA-HCM from Cytokinetics, Incorporated. Dr Lewis has received research funding from the National Institutes of Health (R01-HL 151841, R01-HL131029, and R01-HL159514), American Heart Association (15GPSGC-24800006), Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, and SoniVie; honoraria for advisory boards from Pfizer, Merck, Boehringer Ingelheim, Novartis, American Regent, Cyclerion, Cytokinetics, and Amgen; and royalties from UpToDate for scientific content authorship related to exercise physiology. Dr Michels’ institution has received a research grant from Bristol Myers Squibb. Dr Michels has received consultant/advisor fees from Cytokinetics and Bristol Myers Squibb/Myokardia; and Speakers Bureau fees from Bristol Myers Squibb and Pfizer. Dr Oreziak has received investigator fees from Bristol Myers Squibb/MyoKardia; consultant/advisor fees from Biotronik Polska, Abbott Polska; and traveling fees from Hammermed. Dr Owens has received consultant/advisor fees from Cytokinetics, Bristol Myers Squibb/MyoKardia, and Pfizer. Dr Tfelt-Hansen is a consultant for Leo Pharma, MicroPort, and Johnson and Johnson. Dr Watkins has received consultant/advisor fees from Cytokinetics, BioMarin, and BridgeBio. Dr Heitner, Dr Jacoby, Dr Kupfer, Dr Malik, Dr Meng, and Ms Wohltman are employees of Cytokinetics, Incorporated and hold stock in Cytokinetics, Incorporated. Dr Masri has received consultant/advisor fees from Tenaya, Attralus, Cytokinetics, Bristol Myers Squibb, Eidos, Pfizer, Lexicon, Alnylam, Haya, Intellia, and Ionis; and research grants from Ionis, Akcea, Pfizer, Cytokinetics, Ultromics, and the Wheeler Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)