Mavacamten is a novel cardiac-specific myosin ATPase inhibitor. It specifically reduces excessive cross-bridging with actin, which is associated with pathological hypercontractility in hypertrophic cardiomyopathy.
The EXPOLORER-HCM trial evaluated the efficacy and safety of mavacamten in patients with with HCM with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II–III symptoms.
The trial had significantly positive results in favor of mavacamten. Treatment with it improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive HCM.
Randomized, double-blind, placebo-controlled, phase 3 trial
In total, 251 patients were included and were randomized to receive either mavacampten (N=123) or placebo (N=128).
- ≥18 years of age with diagnosed HOCM
- Left ventricular outflow tract [LVOT] gradient ≥50 mm Hg
- LV ejection fraction (LVEF) ≥55%
- New York Heart Association (NYHA) class II-III symptoms
- History of Syncope
- Episode of Sustained VT with exercise within 6 months
≥ 1·5 mL/kg/min increase in pVO 2 + ≥NYHA class reduction or a ≥ 3·0 mL/kg/m pVO2 increase without NYHA class worsening:
37% patients receiving mavacamten met the primary endpoint criteria compared to 17% in placebo group. diff +19·4%, 95% CI 8·7 to 30·1; p=0·0005
Key Secondary Outcomes:
- Post-exercise LVOT gradient:
Patients receiving mavacampten had mean of -47 mmHg change in their LVOT gradient compared to -10 mmHg in patients receiving palcebo. p<0·0001
2. Increase in pVO2 – mL/kg/min:
Up to 1.4 ml/kg/min increase was noted in pVO2 in mavacampten group compared to decrease of 0.1 ml/kg/min pVO2 in placebo group. p=0·0006
Take Home Point:
Mavacamten is the first in class myosine ATPase inhibitor that has showed efficacy in patients with obstructive HCM. Not only has it shown efficacy in treating symptoms but also improves the LVOT gradient and physiology of the heart mechanics.