BMS Presents Robust Mavacamten Results in HCM Ahead of FDA Decision

Published: Apr 04, 2022

By Jazmine Colatriano M.S.

BioSpace

Over the weekend, Bristol Myers Squibb announced results from an extended study to evaluate the long-term effects of taking cardiovascular drug mavacamten. The EXPLORER-LTE was named after the clinical trial from which it stems: EXPLORER-HCM, a Phase III trial that concluded in 2020. The results showed positive outcomes for those who extended their participation for several additional months. This positive outcome was foreshadowed by the success seen in the original EXPLORER-HCM trial.

Mavacamten is currently being investigated for various cardiovascular indications, including symptomatic obstructive hypertrophic cardiomyopathy, or obstructive HCM. Although not currently approved by any regulatory body, the drug is often referred to as “first-in-class” because it addresses the root cause of obstructions. Its mechanism as a cardiac myosin inhibitor means that it reduces the strong interaction between actin and myosin, causing the heart muscles to ease rather than contract tightly.

According to the U.S. Centers for Disease Control, cardiomyopathy affects one out of every five hundred adults, with many contributing genetic and biological components. Within the category of cardiomyopathy, a patient can be diagnosed with either dilated, restrictive or hypertrophic cardiomyopathy. Each of these categories refers to the condition of a patient’s cardiac muscle. An additional category is arrhythmogenic, which is an irregular heartbeat. However, those affected by hypertrophic cardiomyopathy, or a thickened heart muscle, outnumber all other diagnoses.

The EXPLORER-LTE extension study sought to monitor safety and efficacy in long-term use of mavacamten. It is a cohort within a larger study, the MAVA-LTE. With 231 patients enrolled, 200 undergoing 48 weeks of treatment and 67 patients agreeing to stay for 84 weeks, the data set is impressive. Safety was demonstrated, as no adverse events occurred. Efficacy was shown as patients exhibited improved left ventricular outflow tract (LVOT) gradients, N-terminal pro brain natriuretic peptide (NT-proBNP levels) and classification according to the New York Heart Association (NYHA).

The randomized, double-blind, placebo-controlled EXPLORER-HCM clinical trial included 251 participants. Results were presented in 2021, with the same successful endpoints as its successor.

An additional Phase III study to investigate mavacamten as treatment for obstructive HCM, titled VALOR-HCM, recently concluded. This study also supports the findings seen in the EXPLORER-HCM trial, as it involved evaluation of mavacamten as a treatment for severe cases of obstructive HCM. Participants must have also met the criterion to undergo septal reduction therapy (SRT) according to the 2011 American College of Cardiology and American Heart Association standards. As a trusted method to remove obstructions that occur in the left ventricle, SRT and the need for SRT are clearly significant factors in monitoring obstructive HCM clinical trials. Primary and secondary endpoints for this trial included many of the same endpoints sought in the EXPLORER trials, with an added endpoint of reducing a patient’s need for SRT.

The U.S. Food and Drug Administration expects to conclude review of all data supporting the New Drug Approval (NDA) for mavacamten this month. This prediction comes after the agency announced the need for extra review time in late 2021. The need for additional time is attributed to required changes made to BMS’s Risk Evaluation Mitigation Strategy (REMS).