MyoKardia Presents Results from Phase 3 EXPLORER-HCM Clinical Trial of Mavacamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy

EXPLORER-HCM Data Presented During Live Hot Line Session at ESC Congress 2020 with Simultaneous Publication in The Lancet
Presentation Expands on Positive Topline Results Showing Early, Sustained Reductions in Biomarkers of Cardiac Wall Stress and Myocardial InjuryMavacamten Demonstrated Broad Treatment Effect, with Consistent Benefit Across Primary and Secondary Endpoints Among All Prespecified Patient SubgroupsMyoKardia to Host a Virtual Analyst and Investor Event to
Review Data on Monday, August 31 at 8:00 a.m. EDT
BRISBANE, Calif., Aug. 29, 2020 (GLOBE NEWSWIRE) — MyoKardia, Inc. (Nasdaq: MYOK) announced today that 30-week results from its pivotal Phase 3 EXPLORER-HCM clinical trial of mavacamten for the treatment of symptomatic, obstructive hypertrophic cardiomyopathy (HCM) were presented during a live Hot Line session at the European Society of Cardiology Congress 2020 (ESC Congress 2020). Results from the EXPLORER-HCM study were simultaneously published in The Lancet. MyoKardia previously announced topline data from the EXPLORER-HCM study showing that patients treated with mavacamten experienced statistically significant and clinically meaningful improvements in symptoms, functional status and key aspects of quality of life. In addition to meeting the primary and all secondary endpoints, mavacamten was well tolerated with a safety profile similar to placebo. The data presented today and reported in the published manuscript also include mavacamten’s positive impact on reducing cardiac biomarkers associated with poor prognosis and demonstrate the consistency of its therapeutic benefit across multiple prespecified subgroups.“Hypertrophic cardiomyopathy can be a debilitating, chronic and progressive condition in patients, impairing the function of the heart and lowering patients’ quality of life.  Mavacamten is the first therapeutic candidate to target the heart muscle proteins that drive the excessive contractility and impaired relaxation that are hallmarks of HCM with the intent of correcting the abnormal function of the heart. The results from EXPLORER provide clear, convincing evidence of the therapeutic effect of such a targeted mechanism of action; mavacamten was shown to alleviate the obstruction of the left ventricle and improve patients’ symptoms and cardiac function,” said Daniel Jacoby, M.D., Director, Comprehensive Heart Failure Program at the Yale School of Medicine, an investigator in the EXPLORER-HCM study.The randomized, controlled, pivotal EXPLORER-HCM Phase 3 clinical trial enrolled 251 symptomatic, obstructive patients with HCM, most of whom were on standard background HCM therapy. Among the new data presented today, mavacamten treatment was shown to markedly reduce key biomarkers of cardiac wall stress and injury in a pronounced and clinically meaningful way. Serum concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) from baseline to Week 30 were reduced by 80%, to near normal levels, in the mavacamten treatment group relative to placebo. NT-proBNP is a well-established biomarker of cardiac wall stress that has been associated with increased mortality in HCM patients.(1,2) The decrease in NT-proBNP was observed at the earliest timepoint measured (Week 4) and was sustained throughout the 30-week treatment period. Similarly, reductions in cardiac troponin (hs-cTnI) from baseline to Week 30 were 41% greater in the mavacamten-treated cohort compared to placebo. Cardiac troponin I is closely associated with increased incidence of heart failure, atrial fibrillation and death in patients with HCM.(1,3)“The early and durable reductions toward normal levels of well-established biomarkers associated with cardiac wall stress and injury provide us with early indications that mavacamten may be able to reduce risk of serious complications and poor outcomes,” said Jay Edelberg, M.D., Ph.D., Chief Medical Officer. “The reductions in biomarkers seen in the EXPLORER-HCM study are consistent with our observations of mavacamten’s impact on biomarkers across all of our studies of HCM as well as with the hemodynamic and structural benefits that we see taking place in the heart via cardiac imaging. We will be looking to our long-term studies for further evidence of the potential of mavacamten to alter the course of disease by returning the heart to a healthier state.”As previously reported, mavacamten demonstrated a robust treatment effect in the Phase 3 study. The primary endpoint, a composite functional analysis designed to capture the treatment effect of mavacamten relative to placebo on both symptoms and cardiac function, was met with statistical significance (p=0.0005).  Additionally, mavacamten demonstrated beneficial results (p<0.0006) for all secondary endpoints: post-exercise left ventricular outflow tract (LVOT) peak gradient, peak VO2, New York Heart Association (NYHA) functional classification, the Kansas City Cardiomyopathy Clinical Summary Score (KCCQ-CSS), and the HCM Symptom Questionnaire Shortness of Breath Domain Score.  Data presented today and published in The Lancet reveal that mavacamten’s benefit versus placebo for the primary and all secondary endpoints extended across all prespecified subgroups. Specifically, the reduction in obstruction and the improvements in exercise capacity and clinician (NYHA) and patient (KCCQ and HCMSQ) assessments favoring mavacamten over placebo were highly consistent regardless of age, gender, genetic status, body mass index, background use of beta blockers, or baseline measures of ejection fraction, NYHA class and NT-proBNP.“The consistency of mavacamten’s effects in reducing obstruction and improving symptoms and quality of life across nearly a dozen pre-specified subgroups is a strong testament to the potential broad applicability of this therapy in obstructive HCM,” said Iacopo Olivotto, M.D., of the Cardiomyopathy Unit, Careggi University Hospital and lead clinical investigator for the EXPLORER-HCM clinical trial. “It has been extremely gratifying to directly witness the benefits derived from treatment with mavacamten among my patients who were on study, and I look forward to mavacamten becoming an integral tool in the treatment of patients with obstructive HCM in the future.”Mavacamten was well tolerated and demonstrated safety results similar to placebo, with no new findings observed from those previously reported. Ninety-seven percent of patients enrolled completed the study treatment period. Overall rates of adverse events, serious adverse events, and cardiac adverse events, including atrial fibrillation, were comparable for patients treated with mavacamten and placebo.Mavacamten was granted breakthrough therapy designation from the U.S. Food and Drug Administration in July 2020. MyoKardia plans to submit a New Drug Application for mavacamten to the U.S. Food and Drug Administration (FDA) in the first quarter of 2021.Investor and Analyst Conference Call and Live Webcast
MyoKardia will host a virtual event for investors and analysts to review the 30-week data from EXPLORER-HCM. The live webcast event will begin at 8:00 a.m. EDT / 5:00 a.m. PDT on Monday, August 31 and will include a discussion of the EXPLORER data with Drs. Olivotto and Jacoby, as well as presentations from MyoKardia management regarding the impact of the positive data on MyoKardia and the company’s early commercial preparation efforts.
To access the call, please dial (844) 494-0193 (U.S.) or (508) 637-5584 (international) and reference the conference ID 9917969. A live webcast of the conference call will be available on Investor section of MyoKardia’s website at A replay of the webcast, and accompanying slides, will be available on the MyoKardia website for 90 days following the call.About EXPLORER-HCM
The EXPLORER-HCM Phase 3 trial enrolled a total of 251 patients with symptomatic (NYHA Class II or III), obstructive hypertrophic cardiomyopathy. All participants had measurable LVOT gradient (resting and/or provoked) ≥50 mmHg at baseline.  Patients were randomized on a 1:1 basis to receive individualized once-daily dosing of mavacamten or placebo. Patients started on a dose of 5mg, with up to two opportunities for dose adjustments (to doses of 2.5mg – 15mg) based on a combination of residual LVOT gradient, drug plasma concentration and left ventricular ejection fraction (LVEF) levels.
The primary endpoint for EXPLORER-HCM was a composite functional analysis designed to capture mavacamten’s effect on both symptoms and function. The composite functional endpoint is defined by either (1) the achievement of a ≥1.5mL/kg/min improvement in peak VO2 accompanied by an improvement of ≥1 NYHA functional class, or (2) the achievement of a ≥3.0mL/kg/min improvement of peak VO2 with no worsening in NYHA functional class. In addition to the endpoints reported today, the EXPLORER-HCM study also assessed mavacamten’s effect on patient-reported outcomes, health-related quality-of-life and symptom severity assessments, changes from baseline to Week 30 in echocardiographic indices, circulating biomarkers, cardiac rhythm patterns and accelerometry.About HCM
Hypertrophic cardiomyopathy (HCM) is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of debilitating symptoms and cardiac dysfunction.  HCM is estimated to affect one in every 500 people. The most frequent cause of HCM is mutations in the heart muscle proteins of the sarcomere. In approximately two-thirds of HCM patients, the path followed by blood exiting the heart, known as the left ventricular outflow tract (LVOT), becomes obstructed by the enlarged and diseased muscle, restricting the flow of blood from the heart to the rest of the body (obstructive HCM).  In other patients, the thickened heart muscle does not block the LVOT, and their disease is driven by diastolic impairment due to the enlarged and stiffened heart muscle (non-obstructive HCM).  In either obstructive or non-obstructive HCM patients, exertion can result in fatigue or shortness of breath, interfering with a patient’s ability to participate in activities of daily living.  HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and sudden cardiac death.
About Mavacamten
MyoKardia is developing mavacamten, a first-in-class, oral, allosteric modulator of cardiac myosin, for the treatment of conditions in which excessive cardiac contractility and impaired diastolic filling of the heart are the underlying cause.  Mavacamten is reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance. In clinical and preclinical studies, mavacamten has consistently reduced biomarkers of cardiac wall stress, lessened excessive cardiac contractility and increased diastolic compliance. 
Mavacamten is initially being developed for the treatment of hypertrophic cardiomyopathy (HCM) and has received breakthrough therapy and orphan drug designations for symptomatic, obstructive HCM.  MyoKardia plans to submit a New Drug Application (NDA) for U.S. regulatory approval in this indication in the first quarter of 2021.  Based on mavacamten’s mechanism of action and evidence of therapeutic activity, MyoKardia plans to study mavacamten for the treatment of symptomatic non-obstructive HCM and among a targeted population of patients with heart failure with preserved ejection fraction (HFpEF). About MyoKardia
MyoKardia is a clinical-stage biopharmaceutical company discovering and developing targeted therapies for the treatment of serious cardiovascular diseases. The company is pioneering a precision medicine approach to its discovery and development efforts by 1) understanding the biomechanical underpinnings of disease; 2) targeting the proteins that modulate a given condition; 3) identifying patient populations with shared disease characteristics; and 4) applying learnings from research and clinical studies to inform and guide pipeline growth and product advancement. MyoKardia’s initial focus is on small molecule therapeutics aimed at the proteins of the heart that modulate cardiac muscle contraction to address diseases driven by excessive contraction, impaired relaxation, or insufficient contraction. Among its discoveries are three clinical-stage therapeutics: mavacamten (formerly MYK-461); danicamtiv (formerly MYK-491) and MYK-224. 
MyoKardia’s mission is to change the world for people with serious cardiovascular disease through bold and innovative science.———————————
Kubo, et al.; Circulation; 2011.
Geske, et al.; Journal of the American College of Cardiology; 2013.Seydelmann et al.; Journal of the American Heart Association; 2016.
Forward-Looking Statements
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 returning the heart to a healthier state, the impact of the FDA’s breakthrough therapy designation, or our plan and timing to submit a New Drug Application for mavacamten, 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 June 30, 2020, 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.
Michelle Corral
Executive Director, Corporate Communications and Investor Relations
MyoKardia, Inc.
[email protected] 
Hannah Deresiewicz (investors)
Stern Investor Relations, Inc.
[email protected]
Julie Normant (media)
[email protected]

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