MyoKardia (MYOK) Announces Design of Phase 3 EXPLORER-HCM Study Evaluating Mavacamten in oHCM

May 21, 2018 7:34 AM

MyoKardia, Inc. (Nasdaq: MYOK), a clinical-stage biopharmaceutical company pioneering a precision medicine approach for the treatment of heritable cardiovascular diseases, today announced the design of its pivotal Phase 3 EXPLORER-HCM clinical trial to evaluate the use of mavacamten for the potential treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The company has incorporated input on the study design from the Division of Cardiovascular and Renal Products of the U.S. Food and Drug Administration (FDA), and plans to conduct this single pivotal study along with a long-term extension study to support registration. MyoKardia expects to dose the first patient in the EXPLORER-HCM trial in the second quarter of 2018 and expects that data from the Phase 3 trial will be available in the second half of 2020.

EXPLORER-HCM is a multi-national randomized double-blind study designed to assess the effects of a 30-week treatment of mavacamten versus placebo with a primary endpoint of clinical response. The clinical response endpoint is intended to broadly capture the potential benefits of treatment with mavacamten on how patients feel and function by utilizing both peak oxygen consumption (peak VO2) and New York Heart Association (NYHA) functional classification. Clinical response can be achieved by meeting either of two definitions: 1) an improvement of at least 1.5 mL/kg/min in peak VO2 accompanied by a reduction from baseline of at least one NYHA functional class or 2) an improvement from baseline of 3.0 mL/kg/min or greater in peak VO2 without worsening in NYHA functional class.

“The extensive analysis by our team in designing the EXPLORER-HCM Phase 3 trial, incorporating thoughtful input from the FDA, has resulted in a study designed to provide a robust readout of mavacamten’s safety and efficacy, while minimizing the impact of a placebo effect. Importantly, we believe the innovative design of EXPLORER will allow us to capture the potential benefits of mavacamten across metrics that are of significant importance to patients and clinicians,” said June Lee, M.D., MyoKardia’s Chief Development and Operating Officer. “Should the data from the EXPLORER trial meet our expectations, we believe they will be sufficient to support a marketing application when combined with the safety information we will be gaining in parallel from our long-term extension studies.”

Approximately 220 patients will be enrolled and randomized on a 1:1 basis to receive either mavacamten or placebo. The EXPLORER-HCM trial design includes two opportunities for individualized dose adjustment throughout the 30-week treatment period. Patients in the active treatment arm will start on a once-daily 5mg dose of mavacamten. At Weeks 8 and 14, daily doses may be increased to 10mg or 15mg, or remain unchanged, based on measurements of provoked left ventricular outflow tract (LVOT) gradient conducted at Weeks 6 and 12. A reduction in provoked LVOT gradient under 50 mmHg has been shown in PIONEER to correlate to improvements in several clinical measurements, including NYHA class and peak VO2. All assessments and dose adjustments will be conducted in a blinded fashion. Patients will be allowed to maintain their HCM-related background medications for the duration of the EXPLORER-HCM Phase 3 trial, including beta blockers or calcium channel blockers.

Secondary endpoints in the Phase 3 EXPLORER-HCM trial will include the average change from baseline in post-exercise peak LVOT gradient, NYHA functional class, peak VO2, the proportion of patients achieving post-exercise peak LVOT gradient below 50 mmHg or 30 mmHg at Week 30 and patient-reported outcome measures. Exploratory endpoints will include changes in echocardiographic indices of cardiac structure and function, N-terminal pro b-type natriuretic peptide (NT-proBNP) concentrations, quality of life questionnaire scores and daily physical activity assessed using a wearable accelerometer.

“Symptomatic oHCM patients cope with significant functional limitations and debilitating symptoms that negatively impact their daily lives. The design of our EXPLORER-HCM Phase 3 trial prioritizes the patient’s experience by evaluating mavacamten’s activity in ways that correlate to their daily lives living with oHCM. Measuring peak VO2 tells us how well the heart is working, while the NYHA classification provides information on how patients are functioning during daily activities,” said Marc Semigran, MyoKardia’s Chief Medical Officer. “I’m proud of our team and appreciative of the collaboration from the patient and clinical community as we get ready to embark on this important study.”

Throughout the EXPLORER-HCM study, patients will be monitored for adverse events and certain assessments will be performed. If at any time during the trial, a patient’s plasma concentration is above an upper target range or LVEF falls below the normal range, doses of mavacamten may be decreased. Following the 30-week treatment period and eight-week post-treatment wash-out period, patients will be able to participate in a long-term extension study of mavacamten.

Conference Call and WebcastMyoKardia will host a conference call and live audio webcast today, May 21, 2018, at 8:30 a.m. ET / 5:30 a.m. PT to review the Phase 3 EXPLORER-HCM trial design. The call may be accessed by phone by calling (844) 494-0193 from the U.S. and Canada or (508) 637-5584 internationally and using the conference ID 6896475. The webcast may be accessed live on the Investor Relations section of the Company's website at A replay of the webcast will be available on the MyoKardia website for 90 days following the call.


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