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Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy

Braunwald, Eugene; Saberi, Sara; Abraham, Theodore P; Elliott, Perry M; Olivotto, Iacopo; (2023) Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy. European Heart Journal , 44 (44) pp. 4622-4633. 10.1093/eurheartj/ehad637. Green open access

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Abstract

Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.

Type: Article
Title: Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/eurheartj/ehad637
Publisher version: https://doi.org/10.1093/eurheartj/ehad637
Language: English
Additional information: Copyright © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
Keywords: Pressure gradient, Myectomy, Ejection fraction, Myosin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10183074
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