Inclusion Criteria:

• Has completed the Parent Study through to the EOS Visit within 90 days of signing consent. (Participants who are beyond the 90 day window from EOS Visit may be included in this study pending MyoKardia Medical Monitor approval).
• Participants who prematurely discontinued from the Parent Study or the MAVA LTE study may be considered for inclusion.
• Is able to understand and comply with the study procedures, understand the risks involved in the study, and provide informed consent according to federal, local, and institutional guidelines before the first study-specific procedure.
• Body weight is greater than 45 kg at the Screening Visit or Day 1 (Day 1 weight must be verified prior to dosing).
• Has adequate acoustic windows to enable accurate TTEs (refer to Echocardiography Site Instruction Manual).
• Has documented LVEF ≥ 50% by echocardiography core laboratory read of screening TTE at rest.
• Has safety laboratory parameters within normal limits (according to the central laboratory reference range); however, a participant with safety laboratory parameters outside normal limits may be included if he or she meets all of the following criteria:
  • The safety laboratory parameter outside normal limits is considered by the Investigator to be clinically unimportant;
  • If there is an alanine aminotransferase or aspartate aminotransferase result, the value must be < 3 × the upper limit of the laboratory reference range;
  • The body size–adjusted estimated glomerular filtration rate is ≥ 30 mL/min/1.73 m^2.
• Female participants must not be pregnant or lactating and, if sexually active, must use one of the following highly effective birth control methods from the Screening Visit through 90 days after the last dose of investigational medicinal product (IMP):
  • combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation or progestogen-only hormonal contraception associated with inhibition of ovulation by oral, implantable, or injectable route of administration;
  • intrauterine device (IUD);
  • intrauterine hormone-releasing system (IUS);
  • bilateral tubal occlusion;
  • female is surgically sterile for 6 months or postmenopausal or 1 year. Permanent sterilization includes hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or documented bilateral tubal occlusion at least 6 months prior to Screening. Females are considered postmenopausal if they have had amenorrhea for at least 1 year or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels are in the postmenopausal range.
• In addition to the above contraceptive requirements for female participants, male partners must also use a contraceptive (e.g., barrier, condom, or vasectomy).

Exclusion Criteria:

• Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior and/or is not adequately rate-controlled.
  • Note: participants with persistent or permanent atrial fibrillation who are anticoagulated and adequately rate-controlled are allowed.
• Is currently taking, or has taken within 14 days of Screening, a prohibited medication such as a cytochrome P450 (CYP) 2C19 inhibitor (e.g., omeprazole), a strong CYP 3A4 inhibitor, or St. John’s Wort.
• Has any ECG abnormality considered by the Investigator to pose a risk to participant safety (eg, second degree atrioventricular block type II)
• Has documented obstructive coronary artery disease (> 70% stenosis in one or more epicardial coronary arteries) or history of myocardial infarction.
• Has known moderate or severe (as per Investigator’s judgment) aortic valve stenosis at Screening Visit.
• Has hypersensitivity to any of the components of the mavacamten formulation.
• Has participated in a clinical trial in which the participant received any investigational drug (or is currently using an investigational device) within 30 days prior to Screening, or at least 5 times the respective elimination half-life (whichever is longer), except for participation in MAVERICK-HCM or EXPLORER-HCM. Prior participation in a noninterventional observational study is allowed.
• Has a history of syncope or a history of sustained ventricular tachyarrhythmia with exercise between Parent Study EOS Visit and Screening Visit.
• Has a history of resuscitated sudden cardiac arrest or known history of appropriate implantable cardioverter-defibrillator (ICD) discharge for life-threatening ventricular arrhythmia between Parent Study EOS Visit and Screening Visit.
  • Note: history of anti-tachycardia pacing (ATP) is allowed).
• Currently treated with disopyramide or ranolazine (within 14 days prior to Screening Visit) or treatment with disopyramide or ranolazine is planned during the study.
• Currently treated or planned treatment during the study with a combination of beta blocker and verapamil or a combination of beta blocker and diltiazem.
• Has any acute or serious comorbid condition (e.g., major infection or hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that, in the judgment of the Investigator, could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study.
• History of clinically significant malignant disease that developed since enrollment in the Parent Study:
  • Participants who have been successfully treated for nonmetastatic cutaneous squamous cell or basal cell carcinoma or have been adequately treated for cervical carcinoma in situ or breast ductal carcinoma in situ (DCIS) can be included in the study.
• Is unable to comply with the study requirements, including the number of required visits to the clinical site.
• Is employed by or is a relative of someone employed by MyoKardia, the Investigator, or his/her staff or family.

CMR Substudy Inclusion/Exclusion Criteria:

• Each participant must meet the inclusion/exclusion criteria and be enrolled in the MYK-461-007 study.
• Participants from the MAVERICK-HCM study may participate in the CMR substudy.
• Participants from the EXPLORER-HCM study must have already participated in the CMR substudy.
• In addition, to be included in this substudy participants must not have:
  • An ICD or pacemaker;
  • Atrial fibrillation at the time of scheduled day of CMR;
  • Incidence of major adverse cardiac events (death, stroke, acute myocardial infarction);
  • Incidence of hospitalizations (both cardiovascular [CV] and non-CV);
  • Incidence of heart failure (HF) events (includes HF hospitalizations and urgent emergency room/outpatient visits for HF);
  • Incidence of atrial fibrillation/flutter (new from Screening Visit);
  • Incidence of ICD therapy and resuscitated cardiac arrest;
  • Incidence of ventricular tachyarrhythmias (includes ventricular tachycardia, ventricular fibrillation);
  • Incidence of any AE potentially linked to QT prolongation (Torsade de pointes, CV or sudden death, sustained ventricular tachycardia, ventricular fibrillation and flutter, syncope, and seizures);
  • Frequency and severity of treatment-emergent AEs, treatmentemergent serious AEs, and laboratory abnormalities (including trends in NT-proBNP).

Efficacy and Pharmacodynamics

• Change from baseline in echocardiographic parameters of systolic function (e.g., LVEF) and diastolic function (e.g., peak velocity of early diastolic septal and lateral mitral annular motion [eꞌ], ratio of peak velocity of early diastolic transmitral flow [E] to eꞌ [E/eꞌ], ratio of E to peak velocity of late transmitral flow [A] [E/A], pulmonary artery systolic pressure, left atrium size) over time;
• Change from baseline in resting and post-Valsalva LVOT gradient (EXPLORER-HCM participants only);
• Change from baseline in New York Heart Association (NYHA) functional class over time;
• Change from baseline in NT-proBNP over time;
• Frequency of cardiac transplantation.

Exploratory:

• Change from baseline in arterial pulse wave morphology assessed using an optical biosensor (MAVERICK-HCM participants only);
• Change from baseline over time in patient-reported severity of HCM symptoms as assessed by the HCMSQ score (EXPLORER-HCM participants only);
• Change from baseline in health status as assessed by the EuroQoL five dimensions 5-level questionnaire scores (EXPLORER-HCM participants only).

Pharmacokinetics:

• PK parameters using a population PK approach.