19 March 2021 - - The US Food and Drug Administration has accepted US-based pharmaceutical company Bristol Myers Squibb's (NYSE: BMY) New Drug Application for mavacamten, an investigational, novel, oral, allosteric modulator of cardiac myosin, for patients with symptomatic obstructive hypertrophic cardiomyopathy, the company said.

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of January 28, 2022.

The NDA submission was based on the results of the pivotal Phase 3 EXPLORER-HCM trial, which evaluated mavacamten in patients with symptomatic oHCM versus placebo.

Results from the trial showed that mavacamten demonstrated a robust treatment effect, with clinically meaningful improvements in symptoms, functional status, and quality of life, as well as the ability to relieve left ventricular outflow tract obstruction.

In the EXPLORER-HCM study all primary and secondary endpoints were met with statistical significance.

Mavacamten is an investigational therapy that is not approved for use in any country.

Mavacamten is a first-in-class, oral, allosteric modulator of cardiac myosin, under investigation for the treatment of conditions in which excessive cardiac contractility and impaired diastolic filling of the heart are the underlying cause.

Mavacamten is thought to work by reducing cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.

In clinical and preclinical studies, mavacamten has consistently reduced biomarkers of cardiac wall stress, lessened excessive cardiac contractility, and increased diastolic compliance.

The EXPLORER-HCM Phase 3 trial enrolled a total of 251 patients with symptomatic (NYHA Class II or III), obstructive hypertrophic cardiomyopathy. All participants had measurable left ventricular outflow tract gradient (resting and/or provoked) ≥50 mmHg at baseline.

The primary endpoint for EXPLORER-HCM was a composite functional analysis designed to capture mavacamten's effect on both symptoms and function.

Secondary endpoints were changes from baseline to week 30 in postexercise LVOT gradient, pVO2, proportion of patients with at least one NYHA class improvement, and measures of patientreported outcomes.

Additional endpoints included changes from baseline to Week 30 in echocardiographic indices, circulating biomarkers, cardiac rhythm patterns and accelerometry.

Hypertrophic cardiomyopathy, or HCM, is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of debilitating symptoms and cardiac dysfunction.

HCM is estimated to affect one in every 500 people.