Interim Data Demonstrated Favorable Safety and Activity Profile in Phase 2a Multiple-Ascending Dose Study
Phase 2 Clinical Trial in Targeted Segment of Genetic DCM to Initiate in 1H 2020SOUTH SAN FRANCISCO, Calif., Oct. 28, 2019 (GLOBE NEWSWIRE) — MyoKardia, Inc. (Nasdaq: MYOK), today announced positive interim data from the company’s Phase 2a clinical trial of MYK-491 and will advance MYK-491 into a Phase 2 study in patients with genetic dilated cardiomyopathy (DCM). MYK-491 is MyoKardia’s lead activator candidate designed to increase the contractility of the heart (systolic function) with minimal or no effect on myocardial relaxation and compliance (diastolic function) by acting directly on the proteins in the heart muscle responsible for contraction.  An interim analysis of 26 patients with stable heart failure due to left ventricular systolic dysfunction in the ongoing Phase 2a clinical trial showed that MYK-491 demonstrated improvement in systolic function without impacting diastolic function. These results are consistent with data from MyoKardia’s Phase 1 single-ascending dose studies of MYK-491 in both healthy volunteers and DCM patients. Given the favorable safety profile observed to date, the Phase 2a study has been extended to evaluate higher exposures of MYK-491.  “MYK-491 is improving the heart’s ability to contract, without seeming to affect how the heart relaxes and fills by targeting the heart muscle’s motor protein, myosin. This represents a potentially best-in-class therapeutic profile, and it is what we have been aiming for in order to help patients with certain types of systolic dysfunction, in which their hearts are unable to pump with sufficient force to meet the body’s needs,” said Jay Edelberg, M.D., Ph.D., MyoKardia’s Senior Vice President of Clinical Development. “The data obtained in this Phase 2a trial have satisfied our pre-specified criteria for advancing MYK-491 into later stages of development.”MyoKardia plans to advance MYK-491 into a Phase 2 clinical trial in DCM patients with certain genetic mutations of the cardiac sarcomere in the first half of 2020 and continues to evaluate additional targeted patient populations for potential development. In addition to the clinical data reported to date, MYK-491 was shown in biochemical studies to activate myosin-actin cross-bridge formation in the setting of multiple pathogenic DCM mutations, as well as in genetically normal background, and in preclinical studies to improve myocardial contractility without impairing the heart’s ability to relax and fill.“By looking initially at a relatively homogenous and well-defined population of DCM patients with sarcomeric genetic mutations, where the mechanism underpinning disease closely matches the mechanism of MYK-491, we expect that this study will markedly add to our understanding of the potential benefits of MYK-491 in patients with significant unmet need. The resulting data set will allow us to learn more about biomarkers, dosing and patient response,” said Marc Semigran, MyoKardia’s Senior Vice President, Medical Sciences. “Data from our planned Phase 2 study in genetic DCM will inform further segmentation of the broader systolic heart failure patient population and enable efficient late-stage development efforts.”Dilated cardiomyopathy, regardless of cause, is the most common diagnosis in patients requiring either mechanical circulatory support or a cardiac transplant. There are no approved therapies that target the underlying cause of DCM. Pharmacologic therapies developed over the past 35 years have improved both the prognosis and quality of life of DCM patients, however 5-year mortality still approaches 50 percent in community-based studies.^1,2 Genetic abnormalities contributing to DCM are estimated to be present in about 30-40% of DCM patients, corresponding to an estimated prevalence of 250,000 to 500,000 people in the U.S.^3,4 Further, genetic mutations of the sarcomere impair the ability of the heart muscle proteins to function effectively, leading to progressive worsening of function. Similarly to other DCM patients, genetic DCM patients develop enlargement of the heart, fluid accumulation and shortness of breath.“Dilated cardiomyopathy, a major cause of heart failure, is caused by many different factors and mechanisms, yet treatment approaches today remain much the same across patients,” said Neal Lakdawala, MD, of the Cardiovascular Genetics and Advanced Heart Failure/Cardiomyopathy Program at Brigham and Women’s Hospital, and Assistant Professor of Medicine at Harvard Medical School. “MYK-491 represents a new class of medications targeting a precise mechanism, and the planned trial among genetic DCM patients is a meaningful step on the journey to fulfill the promise of precision medicine in heart failure.”Interim Topline Results from the Phase 2a Clinical Trial of MYK-491
The Phase 2a study was designed to assess safety, tolerability, pharmacokinetics and pharmacodynamics of multiple-ascending oral doses of MYK-491 in patients with stable heart failure with reduced ejection fraction. Patients were randomized to receive either MYK-491 or placebo for one week, during which time they were closely monitored.In 26 patients (20 active; 6 placebo) with stable heart failure, MYK-491 was generally well tolerated. All reported adverse events were mild to moderate. There have been no drug-related serious adverse events, no observations of proarrhythmic effects, and a maximum tolerated dose has not yet been identified.  Asymptomatic, mild, transient increases in troponin, a biomarker of cardiac stress known to fluctuate in heart failure patients, were observed. After seven days of treatment with MYK-491, the average increase in stroke volume, a measure of the amount of blood pumped from the left ventricle, was greater than ten percent relative to baseline, on a placebo-adjusted basis. No impact on measures of diastolic function, or the heart’s ability to relax and fill, was observed.Full data from the ongoing Phase 2a study of MYK-491 will be submitted to an upcoming scientific conference for presentation. About MYK-491
MYK-491 is an oral, small molecule, allosteric activator of myosin. In the heart, myosin is the motor protein that binds to actin to generate the force and movement of contraction. In patients with dilated cardiomyopathy and systolic heart failure, in which the left ventricle of the heart is too distended and weak to adequately pump blood to meet the body’s needs, MYK-491 is intended to increase myosin-actin engagement, thereby targeting the biomechanical defects underlying disease and improving cardiac contractility. Based on data from preclinical research across multiple animal models and Phase 1 studies, MYK-491 may hold potential for controlled increases in the heart’s contractility with minimal impact on relaxation. MYK-491 is currently being studied in a Phase 2a multiple-ascending dose trial in patients with stable heart failure. 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 cardiovascular diseases. MyoKardia’s initial focus is on the development of small molecule therapeutics aimed at the muscle proteins of the heart that modulate cardiac muscle contraction and underlying diseases of systolic and diastolic dysfunction. MyoKardia applies a precision medicine approach to develop its therapeutic candidates for patient populations with shared characteristics, such as causal genetic mutations or disease subtypes. MyoKardia has discovered a pipeline of product candidates directed at diseases driven by excessive contraction, impaired relaxation, or insufficient contraction. Among its discoveries are three clinical-stage therapeutics: mavacamten (formerly 461) in Phase 3 and Phase 2 clinical trials for hypertrophic cardiomyopathies (HCM); MYK-491 in Phase 2 for patients with stable heart failure; and MYK-224, in Phase 1 development for HCM.MyoKardia’s mission is to change the world for people with serious cardiovascular disease through bold and innovative science.Levy, et al, NEJM, 2002Roger, et al, JAMA, 2004Hershberger, et al; Nature, 2013Dal Ferro, et al; Genetics of Dilated Cardiomyopathy Current Knowledge and Future Perspectives. In Sinagra, et al. Dilated Cardiomyopathy: From Genetics to Clinical Management. Springer, 2019
Forward-looking Statement
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 potential of MYK-491, the plans to begin a Phase 2 clinical trial of MYK-491 in genetic DCM patients and the timing of such trial, the ability of data from the Phase 2 clinical trial of MYK-491 to inform late stage clinical testing and the plans to submit full data from the on-going Phase 2a clinical trial of MYK-491, 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, as well as those set forth in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2019, and our other filings with the SEC. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.Contacts: Michelle Corral Corporate Communications & Investor Relations
MyoKardia, Inc.
650-351-4690 Hannah Deresiewicz (investors)
Stern Investor Relations, Inc.
212-362-1200 Julie Normant
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