BMS Announces Positive Phase 3 Results for Mavacamten in Obstructive Hypertrophic Cardiomyopathy

On February 16, 2022, Bristol-Myers Squibb Company (BMS) announced positive results from a Phase 3 clinical trial of mavacamten. Mavacamten is a potential "first-in-class" allosteric inhibitor of cardiac myosin, targeting the underlying pathophysiology of obstructive hypertrophic cardiomyopathy (oHCM). The trial was conducted in symptomatic adult patients with oHCM who were eligible for septal reduction therapy (SRT) and met its primary endpoint at week 16.

oHCM is a chronic progressive disease that causes the heart walls to thicken, making it difficult for the heart to expand properly and fill with blood. This leads to various debilitating symptoms and cardiac dysfunction and is also a common cause of sudden cardiac arrest in young individuals. The most frequent cause of oHCM is mutations in the myocardial proteins of the sarcomere. In patients with oHCM, the left ventricular outflow tract (LVOT), through which blood exits the heart, is obstructed by thickened myocardium. As a result, the condition is also associated with an increased risk of atrial fibrillation, stroke, heart failure, and sudden death, creating an urgent need for new therapies to treat affected patients.

Mavacamten is an innovative oral selective cardiac myosin allosteric modulator that targets the underlying pathophysiology of oHCM, with the potential to reduce excessive cardiac contraction symptoms in patients. In clinical and preclinical studies, mavacamten has been shown to lower biomarkers of cardiac wall stress, reduce excessive myocardial contractility, decrease LVOT gradients, and improve diastolic compliance. The U.S. FDA has granted mavacamten Breakthrough Therapy designation and has accepted its New Drug Application, with a PDUFA date of April 28, 2022. It has been listed by Evaluate as one of the potential blockbuster therapies expected to be approved this year.

This randomized, double-blind, placebo-controlled, multi-center Phase 3 clinical trial was conducted in symptomatic oHCM patients who meet the guideline criteria for septal reduction therapy and were recommended by their physicians for invasive procedures. The trial enrolled over 100 patients, who were randomly assigned to receive either mavacamten or a placebo in a 1:1 ratio.

The primary endpoint is a composite endpoint consisting of the number of patients who decide to undergo septal reduction therapy by or before Week 16, and the number of patients still meeting the criteria for septal reduction therapy at Week 16.

References:

[1] Bristol Myers Squibb Announces Positive Topline Results from Phase 3 VALOR-HCM Trial, Evaluating Mavacamten in Patients with Obstructive Hypertrophic Cardiomyopathy Who are Eligible for Septal Reduction Therapy. Retrieved February 16, 2022, from https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-from-Phase-3-VALOR-HCM-Trial-Evaluating-Mavacamten-in-Patients-with-Obstructive-Hypertrophic-Cardiomyopathy-Who-are-Eligible-for-Septal-Reduction-Therapy/default.aspx

[2] A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy (VALOR-HCM). Retrieved February 16, 2022, from https://clinicaltrials.gov/ct2/show/NCT04349072

(Original text has been abridged)

▽Follow 【WuXi AppTecGermany】WeChat Official Account