Mechanism of action of CAMZYOS

CAMZYOS is a selective, allosteric and reversible cardiac myosin inhibitor. CAMZYOS modulates the number of myosin heads that can enter power-generating states, thus reducing (or in HCM, normalizing) the probability of force-producing systolic and residual diastolic cross-bridge formation. CAMZYOS also shifts the overall myosin population towards an energy-sparing, but recruitable, super-relaxed state (see Figure 1). Excess cross-bridge formation and dysregulation of the super-relaxed state of myosin are mechanistic hallmarks of HCM, which can result in hypercontractility, impaired relaxation, excess energy consumption and myocardial wall stress.

Figure 1: Mechanism of Action A sarcomere is composed of two main protein filaments - the myosin thick filament and actin thin filament. When the myosin thick filaments are attached to the thinner actin filaments, actin-myosin cross bridges are created. Compared to a normal sarcomere, the pathophysiology of hypertrophic cardiomyopathy shows a sarcomere that has hypercontractility due to an excess number of actin-myosin cross bridges. Camzyos targets cardiac myosin and blocks its binding to actin and thereby decreasing the power stroke needed for contraction. The mechanism of action of Camzyos results in attenuated hypercontractility of the sarcomere.

In patients with HCM, myosin inhibition with CAMZYOS normalizes contractility, reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures and biomarkers of cardiac stress, improving symptoms and exercise capacity.