The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to mavacamten (MyoKardia) for the treatment of symptomatic, obstructive hypertrophic cardiomyopathy (HCM).

Mavacamten is a novel, oral, selective allosteric inhibitor of cardiac myosin that reduces excessive cardiac muscle contractility and increases diastolic compliance by inhibiting excessive myosin-actin cross-bridge formation.

The designation is supported by results from the phase 3 EXPLORER-HCM trial that evaluated mavacamten in 251 adult patients with symptomatic, obstructive HCM. Patients were randomized 1:1 to receive either 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). Mavacamten was found to be well tolerated, with a safety profile comparable to placebo.

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“Receipt of Breakthrough Therapy designation from the FDA acknowledges both the significant unmet need among patients with obstructive HCM, for whom there are currently no targeted therapies, and the highly encouraging clinical results generated by mavacamten,” said Tassos Gianakakos, CEO of MyoKardia.

Breakthrough Therapy designation is granted to medicines that treat a serious condition and that demonstrate substantial improvement over available therapies. The Company expects to submit a New Drug Application to the FDA in the first quarter of 2021. The designation allows for expedited review by the Agency.

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