MyoKardia Sees Positive Results in Mid-Stage Heart Trial

Shares of MyoKardia spiked in late trading Thursday after the company revealed positive results from a mid-stage obstructive hypertrophic cardiomyopathy trial. This morning shares of MyoKardia Inc. are climbing again, up more than 5 percent following the opening bell.

On Thursday South San Francisco-based MyoKardia said its Phase II PIONEER-HCM clinical study of its investigational agent mavacamten in patients with symptomatic, obstructive hypertrophic cardiomyopathy (oHCM) hit a number of trial endpoints. The company said two cohorts of patients evaluated dosing levels. Cohort A patients received 10mg, 15mg and 20mg doses. Data shows those dose levels brought about a reduction in the patients’ left ventricular outflow tract (LVOT) gradient before steady-state mavacamten concentrations were reached. That met the primary endpoint of the trial, which was the change in post-exercise peak LVOT gradient from baseline to Week 12.

Mavacamten is a novel, oral, allosteric modulator of cardiac myosin being developed for the treatment of hypertrophic cardiomyopathy (HCM). MyoKardia’s primary care focus is heritable cardiomyopathies, which are a group of rare, genetically-driven forms of heart failure that result from biomechanical defects in cardiac muscle contraction.

Cohort B patients received doses of 2 mg and 5 mg. Patients in that cohort met the primary endpoint of reduction in post-exercise LVOT gradient. However, that cohort failed to hit a few key points. Data released by MyoKardia showed patients on the lowest doses did not achieve a statistically significant increase in Peak VO2, the amount of oxygen during exercise. Writing in Endpoints News John Carroll noted that Peak VO2 levels were regarded as a primary endpoint for mavacamten in the EXPLORER-HCM trial.

MyoKardia Chief Executive Officer Tassos Gianakakos told Endpoints that the company was not surprised in that particular failure. Researchers were looking for the "bottom of an effective range" and have abundant proof-of-concept data to believe it will work when they move to a placebo-controlled registration study, according to Endpoints.

Based on the Phase II results MyoKardia said it believes the ideal dosing for the late-stage trial will be between 5 mg and 15 mg.

"Data from the two cohorts of the PIONEER-HCM study provide us with a greater understanding of the relationship between dosing and the pharmacodynamic effects of mavacamten in treating oHCM patients," Marc Semigran, MyoKardia’s chief medical officer said in a statement. "As we advance into the pivotal Phase III EXPLORER-HCM trial, we feel confident that we can appropriately treat patients with the aim of optimizing the therapeutic effects of mavacamten to improve patients’ symptoms and functional capacity while preserving left ventricular ejection fraction."

MyoKardia expects to begin dosing in its Phase III EXPLORER-HCM study next quarter.

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