MyoKardia Announces Positive Topline Data from its Phase 2 MAVERICK-HCM Clinical Trial of Mavacamten
Achieved Primary Study Objective of Safety and Tolerability in Patients with Non-obstructive HCM
Significant Reductions in Biomarkers of Cardiac Stress Observed in Patients on Treatment vs. Placebo
Data Support Advancement of Mavacamten in Non-obstructive HCM; Regulatory Update Anticipated in the First Half of 2020
Phase 2 Study of Mavacamten Targeting Subgroup of Patients with Diastolic Heart Failure (HFpEF) Anticipated to Begin in the Second Quarter of 2020
Conference Call Today at
“We are encouraged by the evidence from MAVERICK of improved diastolic function in non-obstructive HCM patients with guideline-based measures of diastolic impairment, and by mavacamten’s robust effect in reducing cardiac wall stress in patients across all our HCM studies,” said
Based on the safety and pharmacologic benefits observed in MAVERICK,
“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,” said Stephen Heitner, M.D., Director of the
Heart failure with preserved ejection fraction is a heterogeneous clinical syndrome, which in many patients is characterized by impairment of the left ventricle’s ability to relax and fill during diastole, resulting in insufficient blood flow to meet the body’s needs. HFpEF is estimated to affect approximately three million people in the U.S. and is associated with significant morbidity and mortality. There are currently no approved therapies for HFpEF. The subgroup identified for future evaluation of mavacamten is estimated to include approximately 10-20 percent of the broader HFpEF population.
Phase 2 MAVERICK-HCM Trial – Topline Results
Mavacamten was well tolerated and the observed safety data were consistent with prior studies. The rate of adverse events (AEs) was greater in the mavacamten groups than the placebo group. The majority of AEs reported were mild or moderate in severity and reversible or self-resolving. Serious adverse events (SAEs) occurred twice as frequently in the placebo arm as compared to patients receiving mavacamten. Transient ejection fraction reductions below the protocol-defined threshold of 45% occurred in five participants in the active drug arms.
For the intent-to-treat population, there were no statistically significant differences at 16 weeks between active and placebo groups in exploratory endpoints, with the exception of levels of the biomarker NT-proBNP, which were markedly reduced in patients receiving mavacamten (p=0.004) across both treatment cohorts, as compared to the placebo group. NT-proBNP is a well-established biomarker of cardiac wall stress, and elevated NT-proBNP levels are associated with heart failure-related death or hospitalization, progression to end-stage disease and stroke.
In a pre-specified subgroup representing patients believed to be at higher risk of morbidity and mortality, meaningful trends suggesting clinical benefit were observed for patients on treatment versus placebo across multiple endpoints of symptoms, function, biomarkers of cardiac stress and diastolic compliance.
Additionally, similar trends were observed in a subgroup of patients with elevated cardiac filling pressures (measured by E/e’), suggesting improvement driven by reduced left ventricular pressure, consistent with mavacamten’s targeted mechanism.
“The topline data reported today are important in the advancement of mavacamten across multiple indications. The safety and tolerability data, evidence of mavacamten’s beneficial impact on parameters of diastolic function, and placebo response observations confirm our assumptions and increase our confidence in the EXPLORER-HCM Phase 3 clinical study of mavacamten in obstructive HCM,” said Tassos Gianakakos, Chief Executive Officer of
The Phase 2 MAVERICK-HCM trial was designed to assess the safety and tolerability of a range of exposures over 16 weeks of treatment in patients with symptomatic, non-obstructive HCM. All study participants were required to be diagnosed with non-obstructive HCM, with left ventricular wall thickness either ≥15mm or ≥13mm with a family history of HCM,
A total of 59 participants were enrolled in the study and randomized into one of three groups to receive once-daily doses of mavacamten or placebo. The active mavacamten treatment arms were designed to assess a range of drug concentrations around target levels of 200ng/mL and 500ng/mL. All participants in the active treatment arms began the study receiving 5mg doses of mavacamten. At Week 4, pharmacokinetic (PK) assessments were conducted and doses were adjusted in a blinded fashion per the protocol based on the participant’s assigned cohort. Following the 16-week treatment period, participants were monitored for an additional eight weeks and became eligible to participate in MyoKardia’s MAVA Long-Term Extension (LTE) study.
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About Non-obstructive HCM
Hypertrophic cardiomyopathy is the most common genetic form of heart disease, affecting an estimated one in every 500 people worldwide. There are two main forms of HCM, obstructive HCM and non-obstructive HCM, which often share the same underlying genetic defects in the sarcomere that results in hypercontractility. In non-obstructive HCM, the heart contracts excessively and the left ventricle becomes abnormally thick, restricting the ability of the heart to relax and fill or pump to meet the body’s needs, but no physical obstruction is present in the outflow tract of the left ventricle. Non-obstructive HCM affects an estimated one-third of all HCM patients and presents unique treatment challenges. Patients may progress to a more advanced state of disease than those with obstructive disease before being diagnosed, and there are no approved treatment options available. As non-obstructive HCM progresses, symptoms begin to resemble those of a congestive heart failure patient and heart transplantation may become the only viable treatment option.
About Mavacamten (MYK-461)
Mavacamten is a novel, oral, allosteric inhibitor of cardiac myosin being developed for the treatment of hypertrophic cardiomyopathy (HCM). Mavacamten is intended to reduce cardiac muscle contractility by inhibiting the excessive myosin-actin cross-bridge formation that underlies the excessive contractility, left ventricular hypertrophy and reduced compliance characteristic of HCM.
MyoKardia’s mission is to change the world for people with serious cardiovascular disease through bold and innovative science.
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