Mavacamten Has Positive Impact on Cardiac Structure in Certain Cases of Cardiomyopathy, Data Show

Hypertrophic cardiomyopathy is often an inherited condition and patients may not show symptoms, or those symptoms may be vague, such as fatigue or shortness of breath. The condition can cause varied levels of risk and can result in sudden cardiac death.

The investigational oral therapy mavacamten produced a positive “favorable impact on cardiac structure” for patients with obstructive hypertrophic cardiomyopathy (HCM), according to 48-week data released today by MyoKardia, which is developing the drug.

In HCM, the heart muscle becomes thickened, or “hypertrophied,” without any apparent cause. HCM is often an inherited condition and patients may not show symptoms, or those symptoms may be vague, such as fatigue or shortness of breath. The condition can cause varied levels of risk and can result in sudden cardiac death.

In most cases of HCM, as blood exits the heart through the left ventricle, the left ventricular outflow tract (LVOT) becomes blocked by the enlarged heart muscle, which restricts blood flow to the body; this is known as obstructive HCM. In remaining cases, called non-obstructive HCM, the disease is marked by diastolic impairment and can still limit daily activities.

In PIONEER-OLE, an open label extension study, mavacamten was tested in 12 patients who were at New York Heart Association (NYHA) Class II or III. The study found that the data for mavacamten at 48 weeks “were consistent with prior safety and efficacy observations at the 12-, 24-, and 36-week readouts.”

A statement from MyoKardia said the data demonstrate mavacamten’s safety and tolerability, as well as clinical benefits for patients with obstructive HCM. These include:

  • The LVOT gradient, which measures obstruction of the left ventricle, decreased from baseline with statistical significance among 12 patients. At week 48, resting LVOT for all patients was below 55 mmHg, the guideline threshold for invasive intervention; for 11 of 12, it was below 30 mmHg, the level for diagnosing obstructive HCM.
  • NT-proBNP, a known marker of cardiac wall stress, decreased to normal ranges.
  • NYHA classifications were remeasured at weeks 24 and 48, and 9 of the 12 patients achieved Class I status.
  • Patients received echocardiography to measure interventricular septal (IVS) thickness. As a group, the study patients had mean IVS thickness of 17 mm at baseline, which decreased to 15 mm at 48 weeks after treatment.

“Mavacamten’s continued favorable safety profile and the apparent consistency and durability across so many parameters through one year of treatment are incredibly encouraging and enhance our confidence that mavacamten has the potential to make a lasting impact on the lives of people with HCM,” Jay Edelberg, MD, PhD, senior vice president of Clinical Development, MyoKardia, said in a statement.

Edelberg said that MyoKardia would follow up with a phase 3 study, EXPLORER-HCM, in the first half of 2020.

Non-obstructive HCM

Topline results from a separate study, called MAVERICK-HCM, involving patients with non-obstructive hypertrophic cardiomyopathy, showed the drug met its safety and tolerability targets and brought “significant reductions in biomarkers of cardiac stress observed in patients on treatment vs placebo.”

In a statement, MyoKardia officials said the results would allow them to pinpoint groups of patients with non-obstructive HCM and heart failure with preserved ejection fraction who could be the focus of a future indication for mavacamten. For this population, the company said it would consult with FDA and “expects to provide a regulatory update in 2020.”

“Of all our prior attempts to address the needs of our patients with non-obstructive HCM, for whom there are no effective medical therapies, the MAVERICK-HCM trial provides us with the most encouraging data to date,” Stephen Heitner, MD, director of the Hypertrophic Cardiomyopathy Clinic at Oregon Health and Science University and principal investigator, said in a statement.

“The data reported today are especially promising in that they provide a glimpse into how we may better phenotype this group of patients, and may begin to understand the unpredictability of symptoms,” he said, calling today’s announcement a “springboard” for the next phase of research.

Heitner will present results from PIONEER-OLE on Monday, November 18, 2019, at the American Heart Association Scientific Sessions, being held in Philadelphia.

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