MyoKardia Presents Mavacamten Clinical and Non-Clinical Data at the American Heart Association’s Scientific Sessions 2020
ECHO Data from EXPLORER-HCM Show Mavacamten Treatment Improved Cardiac Structure and Mitral Valve Function in Obstructive Hypertrophic Cardiomyopathy Patients
Markers of Physical Activity from MAVERICK-HCM Accelerometry Data Correlated with Markers of HCM Severity in Non-Obstructive HCM
Non-Clinical Data Show Mavacamten Surrogate Preserved Cardiac Function in Disease Model, Slowing Progression
“These data add detail to the emerging picture of mavacamten’s beneficial impact on the HCM heart, including improvements in cardiac pathophysiology, diastolic function and biomarkers of disease progression,” said
Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study
An exploratory analysis from the Phase 3 EXPLORER-HCM clinical trial of mavacamten for the potential treatment of symptomatic, obstructive HCM investigated the changes from baseline to Week 30 on specific measures of the heart’s structure and function using serial echocardiograms (ultrasounds of the heart).
- Treatment with mavacamten led to statistically significant reductions in left ventricular mass (LVMI), indicating that mavacamten is having an effect on cardiac structure. LVMI has been shown to be a predictor of HCM-related mortality.
- Mavacamten treatment improved left ventricular relaxation (which in turn led to improved cardiac filling pressures). Statistically significant improvements (p<0.0001 for difference from placebo) were achieved across diverse echocardiographic measurements of diastolic function (LA volume index, lateral e’, lateral E/e’, septal e’, and septal E/e’).
- Significantly more mavacamten-treated patients achieved resolution of mitral valve systolic anterior motion (SAM) compared to placebo (80.9% vs. 34.0%; p<0.0001), and 9% achieved resolution of mitral regurgitation (MR) in the mavacamten group vs. none in placebo (p=0.0006). SAM and MR may cause or contribute to obstruction of the left ventricular outflow tract and are known to impact cardiac performance and increase risk of serious cardiovascular complications, such as arrhythmias.
- Mavacamten treatment resulted in significant reductions in cardiac biomarkers of myocardial wall stress and injury compared to placebo. Specifically, there was an 80% greater reduction in NT-proBNP and a 41% greater reduction in cardiac troponin in the mavacamten treatment group vs. placebo.
- Patients with the highest degree of obstruction at baseline achieved greater improvements in echocardiographic parameters and biomarker reductions.
Accelerometer-measured Activity in Non-obstructive Hypertrophic Cardiomyopathy: Patient-generated Activity Measures Correlate With, and are Convolutional Neural Network Predictors of, Clinical Parameters in the MAVERICK-HCM Study
MyoKardia’s Phase 2 MAVERICK-HCM study of mavacamten was the first study to examine quantitative levels of activity in a non-obstructive HCM patient population. As part of the MAVERICK-HCM study, patients were asked to wear ActiGraph GT9X Link wrist-worn monitors for up to 14 days between screening and day 1 and between weeks 12 and 16 to record daily activity. A multitask convolutional neural network (CNN) trained on raw accelerometry, was also used to jointly predict clinical markers of HCM severity.
Markers of physical activity drawn from accelerometry, including average daily accelerometer units (ADAUs) and step count, were associated with standard clinical markers of HCM severity. Out the 59 patients enrolled in MAVERICK-HCM, 50 patients wore the accelerometer for ≥1 compliant day. Patients in MAVERICK-HCM averaged 3,000 steps per day. Results from the accelerometry exploratory analyses showed that higher physical activity correlated with key clinical markers of HCM, including exercise capacity as measured by peak VO2, changes in NT-proBNP levels, and improvements in patient reported outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ), indicating that accelerometry measures may be a useful indicator of drug activity.
Chronic Treatment With A Mavacamten-like Myosin-modulator (MYK-581) Prevents Left-atrial Remodeling, Decreases Cardiac Troponin Leakage, And Blunts Mortality In A Mini-pig Model Of Inherited Hypertrophic Cardiomyopathy
Results from an in vivo study in a genetic mini-pig model of HCM showed that chronic administration of a mavacamten-like myosin-modulator blunted chronic cardiac troponin-T leakage and decreased mortality, both characteristic of HCM progression in this non-obstructive model. In addition, chronic treatment also reduced left-ventricular and prevented left-atrial remodeling, preserving normal left-atrial size as well as atrial myofibrillar structure and function. Taken together, these non-clinical observations provide additional evidence of mavacamten’s activity beyond the reduction of LVOT obstruction and support the emerging clinical evidence of mavacamten’s beneficial effects on overall cardiac structure in the HCM heart.
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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 gradually brining measures of cardiac structure to a normal state, usefulness of raw accelerometry data to predict markers of HCM severity in patients, and the ability of non-clinical observations to provide additional evidence of mavacamten’s activity beyond the reduction of LVOT obstruction, 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.