MyoKardia Presents Results from Phase 3 EXPLORER-HCM Clinical Trial of Mavacamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy
EXPLORER-HCM Data Presented During Live Hot
Presentation Expands on Positive Topline Results Showing Early, Sustained Reductions in Biomarkers of Cardiac Wall Stress and Myocardial Injury
Mavacamten Demonstrated Broad Treatment Effect, with Consistent Benefit Across Primary and Secondary Endpoints Among All Prespecified Patient Subgroups
Review Data on
“Hypertrophic cardiomyopathy can be a debilitating, chronic and progressive condition in patients, impairing the function of the heart and lowering patients’ quality of life. Mavacamten is the first therapeutic candidate to target the heart muscle proteins that drive the excessive contractility and impaired relaxation that are hallmarks of HCM with the intent of correcting the abnormal function of the heart. The results from EXPLORER provide clear, convincing evidence of the therapeutic effect of such a targeted mechanism of action; mavacamten was shown to alleviate the obstruction of the left ventricle and improve patients’ symptoms and cardiac function,” said
The randomized, controlled, pivotal EXPLORER-HCM Phase 3 clinical trial enrolled 251 symptomatic, obstructive patients with HCM, most of whom were on standard background HCM therapy. Among the new data presented today, mavacamten treatment was shown to markedly reduce key biomarkers of cardiac wall stress and injury in a pronounced and clinically meaningful way. Serum concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) from baseline to Week 30 were reduced by 80%, to near normal levels, in the mavacamten treatment group relative to placebo. NT-proBNP is a well-established biomarker of cardiac wall stress that has been associated with increased mortality in HCM patients.(1,2) The decrease in NT-proBNP was observed at the earliest timepoint measured (Week 4) and was sustained throughout the 30-week treatment period. Similarly, reductions in cardiac troponin (hs-cTnI) from baseline to Week 30 were 41% greater in the mavacamten-treated cohort compared to placebo. Cardiac troponin I is closely associated with increased incidence of heart failure, atrial fibrillation and death in patients with HCM.(1,3)
“The early and durable reductions toward normal levels of well-established biomarkers associated with cardiac wall stress and injury provide us with early indications that mavacamten may be able to reduce risk of serious complications and poor outcomes,” said
As previously reported, mavacamten demonstrated a robust treatment effect in the Phase 3 study. The primary endpoint, a composite functional analysis designed to capture the treatment effect of mavacamten relative to placebo on both symptoms and cardiac function, was met with statistical significance (p=0.0005). Additionally, mavacamten demonstrated beneficial results (p<0.0006) for all secondary endpoints: post-exercise left ventricular outflow tract (LVOT) peak gradient, peak VO2,
Data presented today and published in The
“The consistency of mavacamten’s effects in reducing obstruction and improving symptoms and quality of life across nearly a dozen pre-specified subgroups is a strong testament to the potential broad applicability of this therapy in obstructive HCM,” said Iacopo Olivotto, M.D., of the Cardiomyopathy Unit,
Mavacamten was well tolerated and demonstrated safety results similar to placebo, with no new findings observed from those previously reported. Ninety-seven percent of patients enrolled completed the study treatment period. Overall rates of adverse events, serious adverse events, and cardiac adverse events, including atrial fibrillation, were comparable for patients treated with mavacamten and placebo.
Mavacamten was granted breakthrough therapy designation from the
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The EXPLORER-HCM Phase 3 trial enrolled a total of 251 patients with symptomatic (NYHA Class II or III), obstructive hypertrophic cardiomyopathy. All participants had measurable LVOT gradient (resting and/or provoked) ≥50 mmHg at baseline. Patients were randomized on a 1:1 basis to receive individualized once-daily dosing of mavacamten or placebo. Patients started on a dose of 5mg, with up to two opportunities for dose adjustments (to doses of 2.5mg – 15mg) based on a combination of residual LVOT gradient, drug plasma concentration and left ventricular ejection fraction (LVEF) levels.
The primary endpoint for EXPLORER-HCM was a composite functional analysis designed to capture mavacamten’s effect on both symptoms and function. The composite functional endpoint is defined by either (1) the achievement of a ≥1.5mL/kg/min improvement in peak VO2 accompanied by an improvement of ≥1 NYHA functional class, or (2) the achievement of a ≥3.0mL/kg/min improvement of peak VO2 with no worsening in NYHA functional class. In addition to the endpoints reported today, the EXPLORER-HCM study also assessed mavacamten’s effect on patient-reported outcomes, health-related quality-of-life and symptom severity assessments, changes from baseline to Week 30 in echocardiographic indices, circulating biomarkers, cardiac rhythm patterns and accelerometry.
Hypertrophic cardiomyopathy (HCM) is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of debilitating symptoms and cardiac dysfunction. HCM is estimated to affect one in every 500 people. The most frequent cause of HCM is mutations in the heart muscle proteins of the sarcomere. In approximately two-thirds of HCM patients, the path followed by blood exiting the heart, known as the left ventricular outflow tract (LVOT), becomes obstructed by the enlarged and diseased muscle, restricting the flow of blood from the heart to the rest of the body (obstructive HCM). In other patients, the thickened heart muscle does not block the LVOT, and their disease is driven by diastolic impairment due to the enlarged and stiffened heart muscle (non-obstructive HCM). In either obstructive or non-obstructive HCM patients, exertion can result in fatigue or shortness of breath, interfering with a patient’s ability to participate in activities of daily living. HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and sudden cardiac death.
Mavacamten is initially being developed for the treatment of hypertrophic cardiomyopathy (HCM) and has received breakthrough therapy and orphan drug designations for symptomatic, obstructive HCM.
MyoKardia’s mission is to change the world for people with serious cardiovascular disease through bold and innovative science.
- Kubo, et al.; Circulation; 2011.
- Geske, et al.;
Journal of the American College of Cardiology; 2013.
- Seydelmann et al.;
Journal of the American Heart Association; 2016.
Statements we make in this press release may include statements which are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements regarding the clinical and therapeutic benefit and future potential of mavacamten, the ability of our long-term studies to provide further evidence of mavacamten’s potential to alter the course of disease by returning the heart to a healthier state, the impact of the FDA’s breakthrough therapy designation, or our plan and timing to submit a New Drug Application for mavacamten, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, risks associated with the development and regulation of our product candidates and any ongoing effects of the COVID-19 pandemic, as well as those set forth in our Quarterly Report on Form 10-Q for the quarter ended
Executive Director, Corporate Communications and Investor Relations
Stern Investor Relations, Inc.
Source: MyoKardia, Inc.