MyoKardia Presents 36-week Data from PIONEER-OLE Study of Mavacamten at the European Society of Cardiology Congress 2019

Durability of Mavacamten's Safety and Efficacy Profile Demonstrated through Nine Months in this Study of Patients with Symptomatic, Obstructive HCM

Statistically Significant Changes in Key Biomarkers Maintained, Indicative of Potential Improvements in Cardiac Function and Favorable Impact on Long-Term Disease Burden

PARIS and SOUTH SAN FRANCISCO, Calif., Aug. 31, 2019 (GLOBE NEWSWIRE) -- MyoKardia, Inc. MYOK today presented positive data from the company's PIONEER open-label extension (OLE) study of mavacamten for the treatment of symptomatic, obstructive hypertrophic cardiomyopathy (HCM) at the European Society of Cardiology (ESC) Congress 2019, in Paris, France.   

The PIONEER-OLE study enrolled thirteen patients from the Phase 2 PIONEER-HCM study of mavacamten, and twelve patients were evaluable at 36 weeks. Patients received once-daily oral doses of mavacamten individually adjusted to target concentrations to eliminate the obstruction of the left ventricular outflow tract (LVOT). Mavacamten treatment resulted in reductions in patients' resting and provoked LVOT gradient while maintaining a left ventricular ejection fraction (LVEF) above 55% at all times of assessment during the study through week 36. 

"The data from our PIONEER-OLE study continue to demonstrate mavacamten's potential to make a substantial difference in the lives of patients.  As mavacamten acts to reduce the excessive contractility and improve ventricular filling of the HCM heart, patients are reporting feeling better, and the obstruction of the left ventricle has been consistently reduced or eliminated," said June Lee, M.D., Chief Development Officer. "Given the chronic and progressive nature of HCM, we are particularly encouraged by the long-term durability of the safety and efficacy profile, as well as the sustained changes in multiple biomarkers of cardiac stress and diastolic filling pressures moving toward normal levels through 36 weeks of mavacamten treatment." 

PIONEER-OLE 36-week Results
The PIONEER-OLE study was initiated in May 2018 following the conclusion of the PIONEER-HCM Phase 2 clinical trial, to examine the long-term safety and effectiveness of mavacamten.  Data from twelve patients with symptomatic, obstructive HCM at 36 weeks of treatment with mavacamten were presented today.  Mavacamten was well tolerated throughout the treatment period, with no cardiac-related adverse events (AEs) attributed to study drug.   The longest continual duration of mavacamten treatment is now 1.3 years.

Patients received once-daily oral doses of 5 mg mavacamten at study start with an individualized dose adjustment at Week 6 to a dose of 5 mg, 10 mg, or 15 mg aimed at eliminating the obstruction of the left ventricular outflow tract, while maintaining LVEF above normal range. Eleven patients remained on background beta blocker medications. 

Patients entered the PIONEER-OLE study with a mean baseline resting LVOT gradient, a measure of obstruction, of 67.3 mmHg and a mean provoked LVOT gradient of 89.9 mmHg.  Mavacamten reduced or eliminated resting LVOT gradient to a mean of 21.1 mmHg and provoked LVOT gradient to a mean of 31.5 mmHg at Week 36 without reducing left ventricular ejection fraction (LVEF) below normal (50%). 

PIONEER-OLE: Observed Mean Values (SD)

Reductions or elimination of LVOT obstruction has been demonstrated to be a good predictor for improvements in patient symptoms and exercise capacity.  Per protocol, an assessment of New York Heart Association (NYHA) classification is conducted at baseline and Weeks 12, 24, and 48. The 24-week assessment of patient symptoms and function showed 10 of the 13 evaluable patients achieved an improvement of at least one class, and 9 out of 13 achieved asymptomatic NYHA classification (Class I).

A number of key biomarkers of cardiac stress and filling pressure continue to show significant improvements with mavacamten treatment. 

• NT-proBNP, an established circulating blood marker of cardiac wall stress, decreased approximately 10-fold to ranges closer to normal (considered less than 125 pg/mL).  At baseline, the mean NT-proBNP for the 13 patients enrolled in PIONEER-OLE was 1836 pg/mL, and at Week 36 the mean value for 12 evaluable patients was 186 pg/mL.
• E/e', a non-invasive marker of left ventricular filling pressure, decreased from 12.8 to 8.5 at Week 36 among the 12 patients evaluable for response. A normal range of E/e' is less than 8.  E/e' is considered a key measure of diastolic compliance and is an indicator of the left ventricle's ability to relax and fill.  
• Investigators also observed that left atrial (LA) volume index decreased with mavacamten treatment from 40.9 mL/m² to 30.4 mL/m² at week 36.  The LA volume index increases when pressure is elevated and decreases when filling pressure in the left ventricle returns to normal levels, typically in the range of 16-34 mL/m².  Elevated left atrial volume may be associated with increased risk of atrial fibrillation in HCM patients.

PIONEER-OLE: Biomarker Measurements, Mean (SD)

            *p<0.01

These data were presented today in an oral presentation titled "Long-term safety and effectiveness of mavacamten in symptomatic obstructive hypertrophic cardiomyopathy patients: update from the PIONEER open-label extension (PIONEER-OLE) study" (abstract #228) by Andrew Wang, M.D. of Duke University during the Novel Therapeutic Targets in Hypertrophic Cardiomyopathy session at the European Society of Cardiology Annual Meeting.

In addition to the 36-week PIONEER-OLE data, MyoKardia scientists will present additional data from non-clinical studies related to mavacamten during ESC. On September 2, a poster (#P4465) characterizing diastolic effects of mavacamten's mechanism will be presented during Poster Session 5: Mechanisms Underlying Pharmacotherapy.  Another poster (#P6341) detailing a feasibility study for measuring exercise intolerance associated with diastolic dysfunction in a rodent model will be presented on September 3 during Poster Session 7 in the Heart Failure Basic Science section. 

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 (MYK-461)
Mavacamten is a novel, oral, allosteric modulator of cardiac myosin being developed for the treatment of hypertrophic cardiomyopathy (HCM). Mavacamten is intended to reduce cardiac muscle contractility by inhibiting the excessive myosin-actin cross-bridge formation that underlies the excessive contractility, left ventricular hypertrophy and reduced compliance characteristic of HCM.  MyoKardia is currently advancing mavacamten in a pivotal Phase 3 clinical trial, known as the EXPLORER-HCM study, in patients with symptomatic, obstructive HCM and a Phase 2 clinical trial, the MAVERICK-HCM study, in patients with symptomatic non-obstructive HCM. Two long-term follow-up studies are also ongoing, the PIONEER open-label extension study of obstructive HCM patients from MyoKardia's Phase 2 PIONEER trial and the MAVA-LTE, an extension study for patients who have completed either the EXPLORER-HCM or MAVERICK-HCM trials. In April 2016, the U.S. FDA granted Orphan Drug Designation for mavacamten for the treatment of symptomatic obstructive HCM. 

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 MYK-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.

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 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, 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 
Senior Director, Corporate Communications and Investor Relations 
MyoKardia, Inc. 
650-351-4690 
ir@myokardia.com 

Hannah Deresiewicz (investors) 
Stern Investor Relations, Inc. 
212-362-1200 
hannah.deresiewicz@sternir.com

Steven Cooper (media) 
Edelman 
415-486-3264 
steven.cooper@edelman.com