Prof. Dr. Sundeep Mishra evaluates Mavacamten, a first-in-line allosteric inhibitor molecule to target the specific molecular defect of hypertrophic cardiomyopathy. He also explores the results of both EXPLORER-HCM and MAVERICK-HCM trials that tested the benefit of this drug.

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Hypertrophic cardiomyopathy (HCM) is a condition in which the septum of the heart becomes thickened without any obvious cause. It can cause symptoms of heart failure, either from abnormal diastolic left ventricular (LV) function or from LV outflow obstruction in patients with the obstructive phenotype (oHCM). Ultimately, it results in the heart being able to pump blood less effectively leading to symptoms of tiredness, leg swelling, and shortness of breath. It may also result in chest pain or fainting.

While some surgical/interventional procedures like septal myomectomy or alcohol septal ablation were available to reduce septal thickness in oHCM, there was practically no reliable therapy to counter-act diastolic dysfunction of non-obstrictive HCM (nHCM) until now.

However, what about nHCM?

A recent phase 2 trial in nHCM, MAVERICK-HCM revealed that there were some benefits of this drug even in this group. The geometric mean NT-proBNP levels declined 53% with Mavacamten compared to 1% with placebo; mean geometric cardiac troponin I concentrations declined by 34% with Mavacamten but increased 4% with placebo.

Side effects

Minor side effects are rather high with the use of this experimental drug as of now although serious side-effects were no different (or even less) than placebo. More worrisome has been a decline in LV function in some patients but it was reversible.

Thus, Mavacamten is the first drug in its class, developed to target the specific molecular defect of hypertrophic cardiomyopathy and preliminary data from the EXPLORER pivotal trial and MAVERICK-HCM trial confirm Mavacamten’s usefulness in both obstructive and non-obstructive HCM. In oHCM, in particular, its ability to relieve dynamic outflow obstruction, control symptoms, and improve quality of life may be a way forward beyond the classical approach.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Sundeep Mishra is a Professor of Cardiology.