SHaRe Registry Data Published in PNAS Demonstrate the Power of Combining Clinical, Genetic and Structural Data to Gain Insight into Hypertrophic Cardiomyopathy

SOUTH SAN FRANCISCO, Calif., July 14, 2016 (GLOBE NEWSWIRE) -- MyoKardia, Inc. (Nasdaq:MYOK), a clinical stage biopharmaceutical company pioneering a precision medicine approach for the treatment of heritable cardiovascular diseases, today announced the publication of an article in the Proceedings of the National Academy of Sciences of the United States of America. The article is the first to examine data from SHaRe, or the Sarcomeric Human Cardiomyopathy Registry, and demonstrates the power of combining clinical, genetic and structural data to gain insight into hypertrophic cardiomyopathy (HCM).

SHaRe is a multi-center, international repository of clinical and laboratory data on individuals and families with genetic heart disease. MyoKardia helped form the registry in 2014.

HCM can result from any one of hundreds of different genetic variants in human β-cardiac myosin, which causes muscle contraction in the heart. However, it has been difficult for researchers to correlate the location of genetic variants with the severity of disease. This study compares the protein structural locations of genetic variants in myosin from patients with HCM and the general population.

In the course of the study, general methods were developed to interrogate the location of genetic changes in protein structures. These methods identified regions of the myosin protein that are enriched for disease-causing alterations, and the analyses suggest that variants in those regions lead to earlier onset of HCM. “These findings provide a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into genetic disease,” said James Spudich, Ph.D., a co-author of the study and the Douglass M. and Nola Leishman Professor of Cardiovascular Disease in the Department of Biochemistry at Stanford University. “These data represent another step in gaining a deeper understanding of the genetic basis of a debilitating disease that affects about one in 500 people.”  

HCM is the most common form of cardiomyopathy. The U.S. Food and Drug Administration has granted MyoKardia Orphan Drug Designation for MYK-461 for treatment of symptomatic obstructive hypertrophic cardiomyopathy.

The published research represents the collaboration of scientists from MyoKardia, Stanford University, Brigham and Women’s Hospital and others.

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation was published online by PNAS on May 31 and appeared in the print edition in June. The findings were presented at the 2016 Society for Molecular Biology and Evolution Conference in early July.

About MYK-461 and PIONEER-HCM
MYK-461 is an orally administered small molecule designed to reduce left ventricular contractility by allosterically modulating the function of cardiac myosin, the motor protein driving heart muscle contraction. MyoKardia has evaluated MYK-461 in three Phase 1 clinical trials, which have been primarily designed to evaluate safety and tolerability of oral doses of MYK-461 and are providing data on its pharmacokinetic and pharmacodynamic profile. These studies assess MYK-461’s engagement of cardiac myosin by measuring reduction in cardiac muscle contractility via echocardiography. In April 2016, the U.S. FDA granted the company Orphan Drug Designation for MYK-461 for treatment of symptomatic oHCM, a subset of HCM.

About Hypertrophic Cardiomyopathy (HCM) and Obstructive Hypertrophic Cardiomyopathy (oHCM)
It is estimated that one in every 500 people in the United States has HCM, the most prevalent form of heritable cardiomyopathy. HCM is defined as an otherwise unexplained thickening of the walls of the heart, known as hypertrophy. The consequences include reduced left ventricular volumes and cardiac output, reduced ability of the left ventricle to expand, and elevated filling pressures. These can all contribute to reduced effort tolerance and symptoms that include shortness of breath and chest pain. HCM is a chronic disease and for the majority of patients, the disease progresses slowly and can be extremely disabling. HCM substantially increases the risk of developing atrial fibrillation that can lead to stroke or malignant ventricular arrhythmias that can cause sudden cardiac death.

There are currently no approved drug products indicated for the treatment of HCM. Patients are typically prescribed one or more drugs (including beta blockers, non-dihydropyridine calcium channel blockers and disopyramide) indicated for the treatment of hypertension, heart failure or other cardiovascular disorders more generally.

Approximately two thirds of all HCM patients have obstruction, either at rest or with provocation like exercise. oHCM is a physiological complication of HCM in which the thickened heart muscle obstructs the left ventricular outflow tract (LVOT). Measured most commonly by non-invasive imaging (echocardiography), oHCM is defined as ≥30 mm Hg pressure gradient across the LVOT.

Symptoms of oHCM can include shortness of breath, chest pain, dizziness, fainting, and palpitations. The presence of obstruction in an HCM patient further increases risk of progression to severe symptoms, and risk of death from heart failure or stroke.

The degree of LVOT obstruction in oHCM patients is a primary criterion for surgical and other invasive interventions (recommended for symptomatic patients with LVOT gradients measured at ≥50 mmHg). Relief of obstruction has been associated with improved symptoms, function and clinical outcomes. Surgical or other invasive interventions, including septal myectomy, an open heart procedure, may be appropriate.  There are no approved drug products indicated for this condition. 

About MyoKardia
MyoKardia is a clinical stage biopharmaceutical company pioneering a precision medicine approach to discover, develop and commercialize targeted therapies for the treatment of serious and rare cardiovascular diseases. MyoKardia’s initial focus is on the treatment of heritable cardiomyopathies, a group of rare, genetically-driven forms of heart failure that result from biomechanical defects in cardiac muscle contraction. MyoKardia has used its precision medicine platform to generate a pipeline of therapeutic programs for the chronic treatment of the two most prevalent forms of heritable cardiomyopathy—hypertrophic cardiomyopathy, or HCM, and dilated cardiomyopathy, or DCM. MyoKardia’s most advanced product candidate, MYK-461, is an orally-administered small molecule designed to reduce excessive cardiac muscle contractility leading to HCM and is currently being evaluated in three Phase 1 clinical trials. A cornerstone of the MyoKardia platform is the Sarcomeric Human Cardiomyopathy Registry, or SHaRe, a multi-center, international repository of clinical and laboratory data on individuals and families with genetic heart disease, which MyoKardia helped form in 2014. MyoKardia believes that SHaRe, currently consisting of data from approximately 10,000 individuals, is the world’s largest registry of patients with heritable cardiomyopathies. MyoKardia’s purpose is to improve the lives of patients and families suffering from cardiovascular disease by creating targeted therapies that can change the course of their condition. For more information, please visit

CONTACT: Investor Contact:
Beth DelGiacco
Stern Investor Relations, Inc.

Media Contact: 
Steven Cooper

MyoKardia, Inc. Logo