Mavacamten: a novel small molecule modulator of β-cardiac myosin for treatment of hypertrophic cardiomyopathy

Expert Opin Investig Drugs. 2020 Nov;29(11):1171-1178. doi: 10.1080/13543784.2020.1821361. Epub 2020 Sep 20.

Abstract

Introduction: Hypertrophic cardiomyopathy (HCM) is a common known monogenetic cardiovascular disorder which frequently leads to symptoms such as dyspnea and exercise intolerance. Current guideline-recommended pharmacotherapies have variable therapeutic responses. Mavacamten, a small molecule modulator of β-cardiac myosin, reduces hypercontractility, a central mechanism in the pathogenesis of HCM. Mavacamten has recently been evaluated in Phase 2 and 3 clinic trials for obstructive and nonobstructive symptomatic HCM.

Areas covered: This article reviews available preclinical and clinical trials assessing the efficacy and safety of Mavacamten for the treatment of symptomatic obstructive and nonobstructive HCM.

Expert opinion: Findings from Phase 2 and 3 trials suggest that Mavacamten represents a very promising new therapy for the treatment of symptomatic patients with HCM. Treatment leads to an improvement in symptomatic and physiologic metrics for symptomatic patients with HCM with minimal adverse events. Patients with obstructive HCM demonstrated a significant improvement in LVOT gradient, NYHA functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ), Overall Summary Score (OSS), and numerical rating scale (NRS) dyspnea scores; and patients with both obstructive and nonobstructive HCM had significant improvement in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.

Keywords: Mavacamten; hypertrophic cardiomyopathy; myosin.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzylamines / administration & dosage
  • Benzylamines / adverse effects
  • Benzylamines / pharmacology*
  • Cardiomyopathy, Hypertrophic / drug therapy*
  • Cardiomyopathy, Hypertrophic / physiopathology
  • Humans
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Uracil / administration & dosage
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*
  • Uracil / pharmacology
  • Ventricular Myosins / metabolism*

Substances

  • Benzylamines
  • MYK-461
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Uracil
  • Ventricular Myosins