The FDA approval was based on data from the Phase III Explorer-HCM trial that showed Bristol Myers Squibb’s Camzyos could decrease the heart’s contractility.
BMS wins approval for camzyos the first cardiac myosin inhibitor targeting obstructive HCM.(Courtesy of nitpicker/Getty Images)
The U.S. Food and Drug Administration greenlit Bristol Myers Squibb’s Camzyos (mavacamten), the first FDA-approved cardiac myosin inhibitor that specifically targets the source of obstructive hypertrophic cardiomyopathy (HCM).
Obstructive HCM is a progressive disease where the heart walls thicken, which increases the difficulty for the heart to expand normally and fill with blood. Mechanistic hallmarks of Obstructive HCM are excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state.
Role of Camzyos
Camzyos is an allosteric and reversible inhibitor selective for cardiac myosin. The drug has been designed to modulate the number of myosin heads that can enter “on actin” states of the nucleotide, which reduces the “probability of force-producing (systolic) and residual (diastolic) cross-bridge formation,” the company said. The drug “shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state.”
The approval was based on data from the Phase III Explorer-HCM trial that showed Camzyos could decrease the heart’s contractility by inhibiting excessive myosin-actin cross-bridge formation. After 30 weeks of treatment, patients in the Phase III trial who received Camzyos demonstrated greater heart improvement than those on placebo.
The primary endpoint of Explorer-HCM was defined as the proportion of patients who achieved either improvement of mixed venous oxygen tension plus improvement in NYHA class. Data showed that after 30 weeks, 37% of Camzyos patients hit the primary endpoint compared to 17% of placebo patients.
Anjali T. Owens, the medical director of the Center for Inherited Cardiac Disease and an assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, said the approval of Camzyos is a “significant milestone” for appropriate symptomatic obstructive HCM patients.
Owens, a lead investigator on the Explorer-HCM study, also noted these patients and their families have been waiting for a new treatment option for the progressive disease for many years.
Samit Hirawat, executive vice president and chief medical officer of global drug development at Bristol Myers Squibb, said the approval of Camzyos builds on “decades of cardiovascular leadership” and reflects the company’s commitment to treating people with cardiovascular disease.
“We are proud to bring this first-of-its-kind medicine to patients, which may help to address an unmet need in the U.S. in the symptomatic NYHA class II-III obstructive HCM treatment landscape,” Hirawat said in a statement.
Adverse reactions occurred in more than 5% of patients in the Explorer-HCM trial, more commonly in the Camzyos group.
Camzyos does come with a boxed warning for the risk of heart failure. BMS noted that Camzyos reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. It is not recommended to treat patients with Camzyos if they have LVEF less than 55%. Camzyos will only be available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).
