Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (SEQUOIA-HCM)

Key Inclusion Criteria:

• Males and females between 18 and 85 years of age, inclusive, at screening.

• Body mass index <35 kg/m2.

• Diagnosed with HCM per the following criteria:

• Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiacdisease and

• Has an end-diastolic LV wall thickness as measured by the echocardiography corelaboratory of:

• ≥15 mm in one or more myocardial segments OR

• ≥13 mm in one or more wall segments and a known-disease-causing genemutation or positive family history of HCM

• Has resting LVOT-G ≥30 mmHg and post-Valsalva LVOT G ≥50 mmHg during screening asdetermined by the echocardiography core laboratory.

• LVEF ≥60% at screening as determined by the echocardiography core laboratory.

• NYHA Functional Class II or III at screening.

• Hemoglobin ≥10g/dL at screening.

• Respiratory exchange ratio (RER) ≥1.05 and pVO2 ≤90% predicted on the screening CPETper the core laboratory.

• Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been onstable doses for >6 weeks prior to randomization and anticipate remaining on thesame medication regimen during the trial. Patients treated with disopyramide mustalso be concomitantly treated with a beta blocker and/or calcium channel blocker.

Key Exclusion Criteria:

• Known or suspected infiltrative, genetic or storage disorder causing cardiachypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).

• Significant valvular heart disease (per investigator judgment).

• Moderate-severe valvular aortic stenosis.

• Moderate-severe mitral regurgitation not due to systolic anterior motion of themitral valve.

• History of LV systolic dysfunction (LVEF <45%) or stress cardiomyopathy at any timeduring their clinical course.

• Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations).

• Has been treated with septal reduction therapy (surgical myectomy or percutaneousalcohol septal ablation) or has plans for either treatment during the trial period.

• Documented paroxysmal atrial fibrillation during the screening period.

• Paroxysmal or permanent atrial fibrillation is only excluded IF:

• rhythm restoring treatment (eg, direct-current cardioversion, atrialfibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤6 months prior to screening.

• rate control and anticoagulation have not been achieved for at least 6 monthsprior to screening.

• History of syncope or sustained ventricular tachyarrhythmia with exercise within 6months prior to screening.

• Has received prior treatment with CK-3773274 or mavacamten.