MyoKardia announced positive topline data from the company’s Phase III pivotal EXPLORER-HCM clinical trial of MYK 461 (mavacamten) for the treatment of patients with symptomatic, obstructive hypertrophic cardiomyopathy (HCM) (clinicaltrials.gov NCT03470545). Mavacamten demonstrated a robust treatment effect: the primary and all secondary endpoints of the EXPLORER trial were met with statistical significance. Mavacamten was well tolerated, and meaningful improvements in symptoms, functional status and quality of life, as well as reduction or elimination in obstruction of the left ventricle, were observed among patients on treatment versus placebo.
The 30-week treatment with mavacamten resulted in a highly statistically significant outcome relative to placebo (p=0.0005) for the primary endpoint in the EXPLORER-HCM trial, a composite functional analysis designed to capture the treatment effect of mavacamten relative to placebo on both symptoms and cardiac function. All secondary endpoints also demonstrated statistically significant and clinically meaningful improvements for mavacamten as compared to placebo.
Secondary endpoints in the EXPLORER-HCM trial evaluated improvements in post-exercise left ventricular outflow tract (LVOT) peak gradient (p<0.0001), New York Heart Association (NYHA) functional classification (p<0.0001), peak VO2 (p=0.0006), the Kansas City Cardiomyopathy Clinical Summary Score (KCCQ-CSS) (p<0.0001), and the HCM Symptom Questionnaire Shortness of Breath Domain Score (p<0.0001). Mavacamten was well tolerated and demonstrated safety results comparable to placebo, with no new findings observed. Ninety-eight percent of patients enrolled completed the study. Of the two percent who dropped out, none were due to reduced ejection fraction or symptoms of heart failure. Overall rates of adverse events, serious adverse events, and cardiac adverse events, including atrial fibrillation, were comparable for patients treated with mavacamten and placebo. Based on these results, MyoKardia CEO Tassos Gianakakos said the company plans to submit the drug for FDA review early next year.