MyoKardia Announces Positive Topline Data from its Phase 2 MAVERICK-HCM Clinical Trial of Mavacamten




SOUTH SAN FRANCISCO, Calif., Nov. 11, 2019 (GLOBE NEWSWIRE) -- MyoKardia, Inc. (Nasdaq: MYOK), today announced topline data from MAVERICK-HCM, the company’s Phase 2 clinical trial of mavacamten in patients with non-obstructive hypertrophic cardiomyopathy (HCM).  The study achieved its primary objective of establishing safety and tolerability of mavacamten in non-obstructive HCM over a treatment period of 16 weeks.  Meaningful reductions in biomarkers of cardiac stress were observed across both mavacamten drug concentration cohorts and clear signals of clinical benefit were noted in a subgroup with elevated cardiac filling pressures and in a pre-specified group of patients at higher risk for morbidity and mortality.

“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 Jay Edelberg, Senior Vice President of Clinical Development at MyoKardia.  “Consistent with our precision medicine approach, the results of MAVERICK have provided us with important insights, including how to identify groups of patients with diseases of diastolic dysfunction and how to best measure clinical benefit.  These data will inform enrollment criteria, dosing, duration and potential endpoints for our planned future clinical trials of mavacamten in non-obstructive HCM and targeted HFpEF patients.”

Based on the safety and pharmacologic benefits observed in MAVERICK, MyoKardia plans to advance mavacamten into additional studies in defined groups of patients with non-obstructive HCM and heart failure with preserved ejection fraction (HFpEF).  For the non-obstructive indication, the company will seek to consult with the U.S. Food and Drug Administration (FDA) on potential pathways to registration and expects to provide a regulatory update in the first half of 2020.  For the targeted HFpEF population, MyoKardia plans to initiate a Phase 2 study in the second quarter of 2020 in a subgroup of patients sharing many characteristics with the subgroups identified in MAVERICK.  Further analysis of the findings from MAVERICK is ongoing, and these data will be submitted for presentation at an upcoming scientific conference. 

“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 Hypertrophic Cardiomyopathy Clinic at Oregon Health & Science University and a principal investigator for the MAVERICK-HCM trial. “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. I am hopeful that this study will prove to be the springboard for the thoughtful development of the next phase of studies aimed at bringing mavacamten, a unique and precise therapy, to our non-obstructive HCM patients and potentially other similar individuals suffering from HFpEF.”

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 MyoKardia.

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, New York Heart Association (NYHA) classifications of Class II or III, and NT-proBNP levels of greater than 300 pg/mL at rest.  Baseline characteristics, such as age, weight, gender, pathogenic mutation status, background beta blocker use, NYHA classification and exercise capacity were evenly distributed between active and placebo arms.

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. (Article from :

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