Mavacamten is a first-in-class small molecule therapeutic that reversibly binds to myosin to directly target the excess contractility and impaired relaxation underlying hypertrophic cardiomyopathy, or HCM.
Hypertrophic Cardiomyopathy (HCM) is a chronic, progressive disease driven by excessive cardiac contractility causing the walls of the heart to thicken and preventing the heart from relaxing and filling. A portion of individuals with HCM will develop the obstructive form of disease, in which the enlarged and diseased muscle blocks the flow of blood from the left ventricle to the rest of the body. Non-obstructive HCM is driven by diastolic impairment due to the enlarged and stiffened heart muscle. HCM is a form of heart failure with preserved ejection fraction (HFpEF), a form of heart failure driven by diastolic dysfunction in which the pumping function of the heart remains intact, but the left ventricle is not able to fill properly with blood.
Currently, there are an estimated 1.1 million patients with HCM in China. Individuals with HCM may develop debilitating symptoms that interfere with daily activities and are more prone to conditions of cardiac dysfunction, such as heart failure, atrial fibrillation, stroke and sudden cardiac death. Of the nearly 6 million patients with HFpEF in China, an estimated 10-20% share similar disease characteristics with non-obstructive HCM.
LianBio is pursuing a registration strategy for mavacamten in China for obstructive HCM, non-obstructive HCM and HFpEF. Obstructive HCM is the most advanced of these indications and MyoKardia reported Phase 3 topline data from a study of mavacamten for the treatment of obstructive HCM in May 2020 in which the primary and all secondary endpoints were met with high statistical significance (p less than 0.0006). A mid-stage study of non-obstructive HCM improved biomarkers of cardiac stress and injury and demonstrated benefit in the those who had the most severe diastolic impairment.
Clinical evidence suggests that mavacamten may be an appropriate treatment option for HFpEF patients whose disease is driven by diastolic dysfunction and shares similar characteristics to that of non-obstructive HCM patients.