MyoKardia transforms inherited heart disease symptoms in midstage trial

human heart
An estimated 70,000 patients could potentially benefit from mavacamten if approved.

MyoKardia just announced that its experimental drug mavacamten improved heart function in patients with an inherited cardiac condition, with eight of 10 showing normal readings after treatment with the drug.

It is the first major clinical test for the South San Francisco biotech's lead drug candidate, which is partnered with Sanofi, and the top-line data had pushed shares up by a third in out-of-hours trading at the time of writing.

Former Fierce 15 company MyoKardia says it is now working on the design of its next trial in patients with symptomatic, obstructive hypertrophic cardiomyopathy (oHCM) which could start later this year and potentially be the basis of a regulatory filing—something it hopes to discuss with the FDA "as soon as possible."

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HCM is a genetic disorder affecting about one in 500 people in which a defect in the proteins that help control cardiac contraction cause the muscle wall in the heart to become thickened. In some patients HCM is relatively benign, but if the wall thickening blocks the flow of blood in the heart, as is the case in oHCM, it can cause severe symptoms and sudden death.

Mavacamten—formerly known as MYK-461—is designed to reduce the contractility of the muscle fibers in the heart. In the phase 2 PIONEER-HCM trial, its effect in patients at the severe end of the oHCM spectrum was assessed using a measure called the left ventricular outflow tract (LVOT) gradient, which is used by physicians to diagnose and monitor HCM.

All 10 evaluable patients in the trial saw their LVOT gradients reduce after 12 weeks' treatment, and in eight these were restored to normal levels, below the diagnostic threshold for oHCM. Added to that, secondary benefits were also seen, including peak oxygen consumption (peak VO2) and improvement on the New York Heart Association (NYHA) scale.

Improvements from baseline were observed at week 12 by at least one NYHA class in seven patients, with two of these patients improving by two classes.

"Going from NYHA Class III to Class I is really impressive from the point of view of patient symptoms…going from fatigue with mild exertion to being completely asymptomatic," said Marc Semigran, M.D., chief medical officer of MyoKardia, on a conference call.

The results seen with the drug are comparable to those achieved with surgery for HCM, he added, noting that this was remarkable given that patients were also not on beta blockers—the primary therapy at the moment. Investors will get a chance to see the data in more detail at the Heart Failure Society of America (HSFA) annual meeting later this year.

The upcoming trial, called EXPLORER-HCM, will use peak VO2 as a primary endpoint and enroll 200 to 250 patients; additional details such as its duration will be revealed later this year. Meanwhile, MyoKardia has a second, low-dose patient cohort in PIONEER-HCM that has completed enrollment and should generate results in early 2018. In that study, patients will be able to continue beta blocker therapy.

The company estimates that about 70,000 oHCM patients could potentially benefit from mavacamten if approved for marketing.