The phase III pivotal trial of mavacamten, an oral, allosteric cardiac myosin modulator for treating symptomatic, obstructive hypertrophic cardiomyopathy, from Myokardia Inc., of Brisbane, Calif., hit its primary and all of its secondary endpoints.

The company stock (NASDAQ:MYOK) was met with enthusiasm May 11, as shares swelled 58.62% to close at $96.90 each. The stock has doubled in value during the past 12 months. On May 13, 2019, shares went for $45.90 each. Even more recently, the stock struggled at about the same level, as on March 16, shares went for $43.50 each.

With positive data in hand from the EXPLORER study, Myokardia said it plans to submit an NDA in the first quarter of 2021. Myokardia is developing mavacamten to treat conditions in which excessive cardiac contractility and impaired diastolic filling of the heart are the underlying cause.

Hypertrophic cardiomyopathy (HCM) is a chronic, progressive disease characterized by excessive contraction of the heart muscle and the reduced ability of the left ventricle to fill, and it can lead to debilitating symptoms and cardiac dysfunction. It affects about one in every 500 people.

Trailing Myokardia is Cytokinetics Inc., of San Francisco. Last September, Cytokinetics released positive data on CK-274, its myosin inhibitor, for treating HCM. The study met its primary and secondary objectives to assess safety and tolerability of single and multiple oral doses. The company plans a phase II trial in patients with obstructive HCM.

EXPLORER’s primary endpoint was a composite functional analysis to capture mavacamten's treatment effect relative to placebo, on both symptoms and function using standards of New York Heart Association class and peak VO2 measurements, respectively. Thirty-seven percent of Mavacamten-treated patients achieved that endpoint, more than double the placebo rate of 17%. That was highly statistically significant with “p” value of 0.005.

Two-hundred and fifty-one patients across 13 countries were treated for 30 weeks, followed by an eight-week washout period. Ninety-eight percent of patients enrolled completed the study. Once the trial ended, more than 95% of eligible patients enrolled in the long-term extension study.

Patients were randomized on 1-to-1 basis to receive individualized once-daily dosing of mavacamten or placebo. Mavacamten dosing started at 5 mg, with two opportunities for dose adjustment based on clinical response, residual left ventricular outflow tract gradient (LVOT) and left ventricular ejection fraction as well as drug plasma concentration.

Mavacamten resulted in a reduction in the LVOT gradient, with about three-quarters of patients showing gradients below 50 mm of mercury, a threshold for an invasive intervention, and almost 60% were below 30%, the lever for diagnosing the obstruction. Sixty-five percent of patients had an improvement in New York Heart Association class vs. 31% with placebo, and 50% of mavacamten patients returned to NYHA Class I status with no symptoms compared to 21% on placebo.

The data show mavacamten was well-tolerated and demonstrated safety results comparable to placebo.

“Over the past decade, we have learned that HCM is a genetically related disease of hypercontractility with too many myosin heads engaging action in the cells of the heart,” Marc Semigran, Myokardia’s senior vice president of medical sciences, said on Monday morning’s conference call. “By binding to myosin and normalizing the number of heads in the dynamic state, mavacamten therapy reduces the hypercontractility and impairment of left ventricular compliance characteristic of HCM.”

Myokardia has had its COVID-19 obstacles, as it recently temporarily suspended enrollment in two ongoing studies, which includes the rollover of patients from its pivotal EXPLORER study of mavacamten into the MAVA-LTE study and enrolling of healthy volunteers in the phase I study testing MYK-224. The company also said new clinical trials planned to start in the second quarter of 2020 will be delayed. Those include the VALOR-HCM phase III trial testing mavacamten as an alternative to septal reduction therapy procedures, the phase II study testing mavacamten in subgroups of patients with heart failure with preserved ejection fraction, and a phase II study of danicamtiv in genetic dilated cardiomyopathy.

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