Therapy Areas: Cardiovascular
US Food and Drug Administration Accepts Supplemental New Drug Application for Camzyos in Symptomatic Obstructive Hypertrophic Cardiomyopathy to Reduce the Need for Septal Reduction Therapy
21 October 2022 - - The US Food and Drug Administration has accepted US-based pharmaceutical company Bristol Myers Squibb's (NYSE: BMY) supplemental new drug application for Camzyos (mavacamten) for an expanded indication to reduce the need for septal reduction therapy, the company said.

Camzyos is currently FDA approved for the treatment of adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms.

The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 16, 2023.

The sNDA submission was based on the results of the Phase 3 VALOR-HCM study, a randomized, double-blind, placebo-controlled study, which evaluated Camzyos in patients with symptomatic, obstructive HCM (NYHA class III-IV) who met the 2011 ACC/AHA guideline criteria for SRT and who have been referred for an invasive procedure.

VALOR-HCM met its primary and all secondary endpoints with a high degree of statistical significance, with no new safety signals observed.

VALOR-HCM (NCT04349072) is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study of patients with symptomatic, obstructive HCM (NYHA class III-IV) who meet guideline criteria for septal reduction therapy and have been referred for an invasive procedure.

The study enrolled 112 patients randomized on a 1: 1 basis to receive mavacamten or placebo.

VALOR-HCM includes three treatment periods over 128 weeks: a 16-week placebo-controlled period, a 16-week active treatment period where all patients received mavacamten and a 96-week long-term extension period where all patients received mavacamten.

The primary endpoint of VALOR-HCM is a composite of the number of patients who decide to proceed with SRT prior to or at Week 16 and the number of patients who remain SRT-guideline eligible (LVOT gradient of ≥50mmHg and NYHA Class III-IV) at Week 16 in the mavacamten group compared with the placebo group.

Key secondary endpoints include impact on exercise gradient LVOT, NYHA Class and Kansas City Cardiomyopathy Questionnaire and biomarkers at Week 16.

Obstructive hypertrophic cardiomyopathy (obstructive HCM) is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can make it difficult for blood to circulate to the rest of the body, leading to the development of debilitating symptoms and cardiac dysfunction.

HCM can be hereditary and can develop at any age. Patients are typically diagnosed in their 40s or 50s, and as many as 50% of patients have a hereditary predisposition.

In obstructive HCM, which is the most common type of HCM, the left ventricular outflow tract where blood leaves the heart becomes obstructed by the enlarged heart muscle.

As a result, obstructive HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and, although rare, sudden cardiac death.

The most frequent cause of obstructive HCM is mutations in the heart muscle proteins of the sarcomere. Obstructive HCM is estimated to affect 400,000-600,000 people worldwide, however many patients remain undiagnosed and/or asymptomatic.

Camzyos (mavacamten) is the first and only cardiac myosin inhibitor approved by the US Food and Drug Administration indicated for the treatment of adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms.

Camzyos is an allosteric and reversible inhibitor selective for cardiac myosin.

Camzyos modulates the number of myosin heads that can enter "on actin" (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation.

Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM.

Camzyos shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with Camzyos reduces dynamic LVOT obstruction and improves cardiac filling pressures.
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