A Systematic Review of Clinical Trials on Mavacamten in Hypertrophic Cardiomyopathy.

Abstract

Introduction: Hypertrophic cardiomyopathy (HCM) is characterised by unusual thickening of the interventricular septum leading to dynamic left ventricular outflow tract obstruction, mitral valve regurgitation, impaired diastolic function and arrhythmias. Mavacamten (MYK-461) is a first-in-class, selective allosteric modulator of cardiac myosin adenosine triphosphatase and received US Food and Drug Administration (FDA) approval on 28 April 2022 to treat symptomatic obstructive HCM (oHCM).

Methods: A systematic search of Medline/PubMed and ClinicalTrials. gov was conducted using advanced search strategies with the terms 'mavacamten/MYK-461' and 'hypertrophic cardiomyopathy/HCM' to identify and include all clinical trials published to date.

Results: The clinical efficacy of mavacamten has been consistently demonstrated in the PIONEER-HCM, MAVERICK-HCM, EXPLORER-HCM, VALOR-HCM, EXPLORER-CN-HCM and HORIZON-HCM clinical trials - there was a notable decrease in the left ventricular outflow tract gradient. Apart from the MAVERICK experiment, which revealed no discernible change in functional class or peak volume of oxygen uptake (pVO₂) in non-oHCM patients, improvements were reported in New York Heart Association functional class, pVO₂ and quality-of-l ife metrics. Except for the PIONEER trial, which didn't report biomarker data such as N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponins, mavacamten significantly reduced biomarkers in all investigations. Additionally, the VALOR trial showed that there was a reduced need for septal reduction therapy. Although systolic dysfunction is a major safety risk that requires careful monitoring, mavacamten was generally well tolerated.

Conclusion: Mavacamten offered a promising, non-invasive pharmacological therapy for patients with symptomatic oHCM, particularly for those who are not candidates for or who have failed conventional treatments.