First-in-Class BMS Cardiomyopathy Drug Mavacamten Receives FDA Approval for Obstructive HCM

On April 29, mavacamten from Bristol-Myers Squibb (BMS) was approved by the FDA for marketing. It is used to treat adult patients with obstructive hypertrophic cardiomyopathy (oHCM) rated as Class II-III according to the New York Heart Association (NYHA) functional classification, aiming to improve exercise capacity and symptoms. This product received the Breakthrough Therapy Designation from the CDE in February this year.

Hypertrophic cardiomyopathy is a chronic progressive disease caused by excessive myocardial contraction and obstruction of left ventricular blood filling, leading to debilitating symptoms and cardiac dysfunction. It can be divided into obstructive or non-obstructive hypertrophic cardiomyopathy, with the most common pathogenic cause being mutations in myocardial sarcomere proteins.

Mavacamten is a potential first-in-class, oral, allosteric modulator of cardiac myosin for the treatment of diseases characterized by excessive cardiac contraction and impaired diastolic filling. It reduces myocardial contractility by inhibiting the excessive formation of myosin-actin cross-bridges, which can lead to excessive myocardial contraction, left ventricular hypertrophy, and reduced compliance.

The FDA approval was based on the pivotal Phase III clinical trial data of mavacamten in patients with symptomatic obstructive HCM. The results showed that both the primary and all secondary endpoints were achieved with high statistical significance (p<0.0006), effectively improving patients' exercise capacity, left ventricular outflow tract gradient (LVOTG), NYHA class, etc.

In August 2020, LianBio obtained the license authorization from MyoKardia, a subsidiary of BMS, for $187.5 million (including a $40 million upfront payment, $147.5 million in milestone payments, and sales royalties) to develop and commercialize mavacamten in mainland China, Hong Kong, Macao, Taiwan, Thailand, and Singapore.

LianBio is currently conducting a randomized, double-blind, placebo-controlled, multi-center Phase III clinical trial to evaluate the efficacy and safety of mavacamten in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy. The study will enroll approximately 81 patients, with the primary endpoint being the change in Valsalva left ventricular outflow tract (LVOT) gradient from baseline to Week 30.