Positive topline data were announced from the phase 3 EXPLORER-HCM trial evaluating mavacamten (MyoKardia) for the treatment of symptomatic, obstructive hypertrophic cardiomyopathy (HCM).

Mavacamten is a novel, oral, selective allosteric inhibitor of cardiac myosin. It works by inhibiting excessive myosin-actin cross-bridge formation, thereby reducing excessive cardiac muscle contractility and increasing diastolic compliance.

The multicenter, double-blind, placebo-controlled trial included 251 adult patients with symptomatic, obstructive HCM. Patients were randomized to receive mavacamten or placebo once daily for 30 weeks. The primary end point of the study was the percentage of patients who achieved a clinical response, defined as the achievement of a ≥1.5mL/kg/min improvement in peak VO2 accompanied by an improvement of ≥1 New York Heart Association (NYHA) functional class, or the achievement of a ≥3.0mL/kg/min improvement of peak VO2 with no worsening in NYHA functional class.  

Results showed that the study met its primary end point; highly statistically significant outcomes were observed with mavacamten compared with placebo (P=.0005). Additionally, mavacamten was associated with statistically significant and clinically meaningful improvements in post-exercise left ventricular outflow tract (LVOT) peak gradient (P <.0001), NYHA functional classification (P <.0001), peak VO2 (P=.0006), the Kansas City Cardiomyopathy Clinical Summary Score (KCCQ-CSS) (P <.0001), and the HCM Symptom Questionnaire Shortness of Breath Domain Score (P <.0001).

“The extraordinary data from the EXPLORER pivotal trial confirm mavacamten’s ability to relieve dynamic outflow obstruction, control symptoms and improve quality of life in patients with hypertrophic cardiomyopathy,” said Iacopo Olivotto, MD, Careggi University Hospital and lead clinical investigator for the EXPLORER-HCM clinical trial. “[…] Mavacamten is the first drug developed to target the specific molecular defect of the disease.” 

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The Company plans to submit a New Drug Application to the Food and Drug Administration in the first quarter of 2021.

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