Mavacamten: A Novel Disease-Specific Treatment for Hypertrophic Cardiomyopathy

Capilupi, Michael J; Frishman, William H.

doi:10.1097/crd.0000000000000433

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…It has been reported that the IC 50 values of Mavacamten in the bovine, human, and rabbit system are 490 nM, 711 nM, and 2140 nM, respectively, indicating a 4-fold selectivity for myocardial myosin [ 176 – 178 ]. Mavakamten is found to reduce contractility through decreasing the activity of adenosine triphosphatase in the heavy chain of myocardial myosin [ 179 ]. Long-term administration results in the inhibition of the development of myocardial cell disorders, myocardial hypertrophy, and myocardial fibrosis, and attenuates the gene expression of profibrotic and hypertrophic in mice featuring heterozygous human mutations in the chain of myosin heavy [ 176 ].…”

Section: Other Drugsmentioning

confidence: 99%

Synthesis and clinical application of new drugs approved by FDA in 2022

Zhang,

Wang,

Sun

et al. 2023

Mol Biomed

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The pharmaceutical industry had a glorious year in 2022, with a total of 37 new drugs including 20 new chemical entities (NCEs) and 17 new biological entities (NBEs) approved by the Food and Drug Administration (FDA). These drugs are mainly concentrated in oncology, central nervous system, antiinfection, hematology, cardiomyopathy, dermatology, digestive system, ophthalmology, MRI enhancer and other therapeutic fields. Of the 37 drugs, 25 (68%) were approved through an expedited review pathway, and 19 (51%) were approved to treat rare diseases. These newly listed drugs have unique structures and new mechanisms of action, which can serve as lead compounds for designing new drugs with similar biological targets and enhancing therapeutic efficacy. This review aims to outline the clinical applications and synthetic methods of 19 NCEs newly approved by the FDA in 2022, but excludes contrast agent (Xenon Xe-129). We believe that an in-depth understanding of the synthetic methods of drug molecules will provide innovative and practical inspiration for the development of new, more effective, and practical synthetic techniques. According to the therapeutic areas of these 2022 FDA-approved drugs, we have classified these 19 NCEs into seven categories and will introduce them in the order of their approval for marketing.

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Section: Other Drugsmentioning

confidence: 99%

Synthesis and clinical application of new drugs approved by FDA in 2022

Zhang,

Wang,

Sun

et al. 2023

Mol Biomed

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Aficamten—A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy

Patel,

Wang,

Naidu

et al. 2023

Cardiology in Review

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Hypertrophic cardiomyopathy is an under-recognized disease with a genetic component that results in abnormal and often asymmetric thickening of the left ventricle in addition to decreased compliance and progressive fibrosis of the myocardium. It further poses significant complications related to dynamic left ventricular outflow obstruction over time in a significant majority. The medical management of obstructive hypertrophic cardiomyopathy has evolved over the decades as our understanding has grown. Traditionally, the mainstay in management has included the use of various negative inotropic agents. In contrast, the cardiac myosin inhibitors, aficamten and mavacamten, are novel therapies targeting cardiac contractility at the sarcomere level that have demonstrated improvement in clinical outcomes for patients, and mavacamten (Bristol Myers Squibb, Inc.) has now been approved by the Food and Drug Administration for the treatment of symptomatic obstructive HCM. Aficamten (Cytokinetics, Inc.) is the second in class cardiac myosin inhibitor that is currently being evaluated in ongoing phase III clinical trials, and is the subject of this review.

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New Era: Mavacamten for Obstructive Hypertrophic Cardiomyopathy

Al‐Horani

Woodland

2023

CHAMC

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Obstructive hypertrophic cardiomyopathy results from asymmetric septal hypertrophy which eventually obstructs the outflow of the left ventricle. Obstructive hypertrophic cardiomyopathy is linked to mutations in genes that encode for sarcomere proteins including actin, &#946:myosin heavy chain, titin, and troponin. The mutations lead to structural abnormalities in myocytes and myofibrils causing conduction irregularities and abnormal force generation. Obstructive hypertrophic cardiomyopathy is a chronic disease that worsens over time and patients become at higher risk to develop atrial fibrillation, heart failure, and stroke. Up until recently, there were no disease-specific medications for obstructive hypertrophic cardiomyopathy. Nevertheless, the US Food and Drug Administration approved mavacamten on April 28, 2022, for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (New York Heart Association class II to III) in adults to improve functional capacity and symptoms. Its approval was based on data from EXPLORER-HCM and EXPLORER-LTE (NCT03723655). Mavacamten is a novel, first-in-class, orally active, allosteric inhibitor of cardiac myosin ATPase, which decreases the formation of actin-myosin cross-bridges, and thus, it reduces myocardial contractility, and it improves myocardial energetics. It represents a paradigm-shifting pharmacological treatment of obstructive hypertrophic cardiomyopathy. In this review, we describe its chemical and mechanistic aspects as well as its pharmacokinetics, adverse effects and warnings, potential drug-drug interactions, and contraindications.

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Mavacamten: A Novel Disease-Specific Treatment for Hypertrophic Cardiomyopathy

Cited by 3 publications

References 19 publications

Synthesis and clinical application of new drugs approved by FDA in 2022

Synthesis and clinical application of new drugs approved by FDA in 2022

Aficamten—A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy

New Era: Mavacamten for Obstructive Hypertrophic Cardiomyopathy

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