Mavacamten (MyoKardia) improves heart function and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), according to results of the EXPLORER-HCM trial presented in a Hot Line session at ESC Congress 2020 (Virtual, 29 August–1 September). The findings were published simultaneously in The New England Journal of Medicine.
“The results of this pivotal trial support a role for disease-specific therapy for obstructive hypertrophic cardiomyopathy which treats the cause instead of just managing symptoms,” said principal investigator Iacopo Olivotto of Careggi University Hospital, Florence, Italy.
EXPLORER-HCM was a pivotal, global, phase 3, randomised, placebo-controlled clinical trial that tested the efficacy and safety of mavacamten in treating symptomatic obstructive HCM. A total of 251 patients received once daily mavacamten or placebo for 30 weeks. The endpoints were chosen to examine exercise capacity, symptoms, LVOT obstruction, functional status, and quality of life.
The primary endpoint assessed the treatment effect of mavacamten at week 30 relative to placebo on both symptoms and cardiac function. It was defined as achieving 1) ≥1.5 mL/kg/min improvement in peak oxygen consumption (peak VO2) and ≥1 New York Heart Association (NYHA) class reduction OR 2) ≥3.0 mL/kg/min improvement in peak VO2 and no worsening of NYHA class.
Secondary endpoints included change from baseline to week 30 in post-exercise LVOT gradient and patient-reported outcomes such as the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and HCM Symptom Questionnaire-Shortness-of-Breath (HCMSQ-SoB) subscore. At week 30, 45 (36.6%) patients on mavacamten met the primary composite endpoint versus 22 (17.2%) on placebo (p=0.0005).
All secondary endpoints, including post-exercise LVOT gradient and patient-reported outcomes, also demonstrated statistically significant improvements for mavacamten as compared to placebo (all p<0.0006). Safety and tolerability with mavacamten were similar to placebo. Some 11 serious adverse events were reported in 8.1% of patients on mavacamten versus 20 events in 8.6% of patients on placebo.
Serious cardiac adverse events occurred in four patients treated with mavacamten (two atrial fibrillation, two stress cardiomyopathy), and four in the placebo group (three atrial fibrillation, one atrial fibrillation and congestive heart failure).
Olivotto said: “The totality and consistency of the results showed benefit of mavacamten treatment compared to placebo in patients on background HCM therapy. Mavacamten improved functional capacity, LVOT gradient, symptoms, and key aspects of quality of life in patients with obstructive HCM and was generally well tolerated.”