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Clinical Trial Design

SEQUOIA-HCM: The largest-to-date Phase 3 clinical trial in oHCM1,2

CLINICAL TRIAL DESIGN

Evaluated efficacy and safety in a randomized, double-blind, placebo-controlled study over 24 weeks2

  • Patients taking MYQORZO™ initiated treatment at 5 mg orally once daily and were titrated as needed using echocardiographic guidance by 5-mg increments to a maximum dose of 20 mg once daily based on patient response2*
SEQUOIA-HCM trial design
Cyclical patient icon

85% of patients with symptomatic oHCM enrolled in SEQUOIA-HCM were on ≥1 oHCM standard of care therapy (beta blockers, calcium channel blockers, and/or disopyramide)2†

ENDPOINTS

The SEQUOIA-HCM trial met all of its prespecified clinical endpoints1-3

Person walking on treadmill icon

PRIMARY ENDPOINT

P Value

Change in peak oxygen consumption (peak VO2) as assessed during cardiopulmonary exercise testing (baseline to Week 24)

P<0.0001

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SECONDARY ENDPOINTS‡

P Value

Mean change in KCCQ-CSS (baseline to Week 24)

P<0.0001

Proportion of patients with ≥1 NYHA Class improvement (baseline to Week 24)

P<0.0001

Mean change in Valsalva LVOT gradient (baseline to Week 24)

P<0.0001

Proportion of patients with LVOT gradient post-Valsalva maneuver <30 mmHg (at Week 24)

P<0.0001

Mean duration of septal reduction therapy eligibility (during 24 weeks of treatment)§

P<0.0001

Mean change in KCCQ-CSS (baseline to Week 12)

P<0.0001

Proportion of patients with ≥1 NYHA Class improvement (baseline to Week 12)

P<0.0001

Mean change in Valsalva LVOT gradient (baseline to Week 12)

P<0.0001

Proportion of patients with LVOT gradient post-Valsalva maneuver <30 mmHg (at Week 12)

P<0.0001

Mean change in total workload as assessed during cardiopulmonary exercise testing (baseline to Week 24)

P<0.0001

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SELECT EXPLORATORY AND ADDITIONAL ENDPOINTS EVALUATED

  • Distribution of NYHA Functional Classes over time
  • Mean change in left atrial volume index (LAVI) (baseline to Week 24)
  • Mean change in LV maximal wall thickness (baseline to Week 24)
  • Mean change in NT-proBNP (baseline to Week 24)

Inclusion and exclusion criteria in SEQUOIA-HCM

BASELINE PATIENT CHARACTERISTICS

The majority of patients enrolled in SEQUOIA-HCM were already being treated with standard of care oHCM treatment2

Baseline characteristics2,5MYQORZO
(n=142)		Placebo
(n=140)
Age, mean (years)59.259.0
Sex, female56 (39.4%)59 (42.1%)
Race
White108 (76.1%)115 (82.1%)
Asian29 (20.4%)25 (17.9%)
Black3 (2.1%)0
Other2 (1.4%)0
Geographic region
North America49 (34.5%)45 (32.1%)
China24 (16.9%)22 (15.7%)
Rest of the world69 (48.6%)73 (52.1%)
Medical history
Hypertension75 (52.8%)70 (50.0%)
Family history of HCM41 (28.9%)34 (24.3%)
Known HCM-causing gene mutation24 (16.9%)25 (17.9%)
Paroxysmal atrial fibrillation21 (14.8%)20 (14.3%)
CAD19 (13.4%)16 (11.4%)
Diabetes14 (9.9%)9 (6.4%)
Permanent atrial fibrillation2 (1.4%)1 (0.7%)
85 percent of patients with symptomatic oHCM enrolled in SEQUOIA-HCM were on greater or equal to 1 oHCM standard of care therapy
Background HCM therapy
Beta blocker86 (60.6%)87 (62.1%)
Calcium channel blocker44 (31%)35 (25%)
Disopyramide16 (11.3%)20 (14.3%)
None19 (13.4%)22 (15.7%)
ICD22 (15.5%)17 (12.1%)
KCCQ-CSS, mean score7674
Patients were symptomatic (greater than 75 percent of patients NYHA Functional Class II)
NYHA FC
II108 (76.1%)106 (75.7%)
III34 (23.9%)33 (23.6%)
IV01 (0.7%)
NT-proBNP, median818.0 pg/mL691.5 pg/mL
High-sensitivity cardiac troponin I, median12.9 ng/L11.5 ng/L
Patients were severely obstructed (mean 83 mmHg)
Echocardiographic variables, mean
LVOT gradient post-Valsalva maneuver82.9
mmHg		83.3
mmHg
Resting LVOT gradient54.8
mmHg		55.3
mmHg
LVEF74.8%74.8%
Maximal LV wall thickness20.7 mm21.0 mm
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Baseline characteristics were well balanced between the 2 treatment arms3

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*A response was defined as a decrease in Valsalva LVOT gradient to <30 mmHg and maintained LVEF ≥55%.2

†Stabilized on background therapy for >6 weeks.3

‡The 10 prespecified secondary endpoints in the SEQUOIA-HCM trial were tested hierarchically in the order presented here (proceed only if P<0.05). However, data and presentations on subsequent pages based on these endpoints are not presented in hierarchical order.1,3

§Septal reduction therapy eligibility defined by NYHA FC III-IV and an LVOT gradient ≥50 mmHg (at rest or post-Valsalva maneuver).3

ALT=alanine aminotransferase; AST=aspartate aminotransferase; CAD=coronary artery disease; CPET=cardiopulmonary exercise test; ECG=electrocardiogram; eGFR=estimated glomerular filtration rate; FC=Functional Class; HCM=hypertrophic cardiomyopathy; ICD=implantable cardioverter-defibrillator; KCCQ-CSS=Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score; LV=left ventricular; LVEF=left ventricular ejection fraction; LVOT=left ventricular outflow tract; MI=myocardial infarction; NT-proBNP=N-terminal pro–B-type natriuretic peptide; NYHA=New York Heart Association; oHCM=obstructive hypertrophic cardiomyopathy; RER=respiratory exchange ratio; TBL=total bilirubin; ULN=upper limit of normal; VO2=oxygen consumption.

References: 1. Coats CJ, Maron MS, Abraham TP, et al. Exercise capacity in patients with obstructive hypertrophic cardiomyopathy: SEQUOIA-HCM baseline characteristics and study design. JACC Heart Fail. 2024;12(1):199-215. doi:10.1016/j.jchf.2023.10.004 2. MYQORZO (aficamten). Prescribing information. Cytokinetics; 2025. 3. Maron MS, Masri A, Nassif ME, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. N Engl J Med. 2024;390(20):1849-1861. doi:10.1056/NEJMoa2401424 4. Supplement to: Maron MS, Masri A, Nassif ME, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. N Engl J Med. 2024;390(20):1849-1861. doi:l0.1056/NEJMoa2401424 5. Data on file. South San Francisco, CA. Cytokinetics, Inc; 2024.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF HEART FAILURE

MYQORZO reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction.

Echocardiogram assessments are required prior to and during treatment with MYQORZO to monitor for systolic dysfunction. Initiation of MYQORZO in patients with LVEF <55% is not recommended. Decrease the dose of MYQORZO if LVEF is <50% and ≥40%. Interrupt the dose of MYQORZO if LVEF <40% or if the patient experiences heart failure symptoms or worsening clinical status due to systolic dysfunction.

Because of the risk of heart failure due to systolic dysfunction, MYQORZO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the MYQORZO REMS Program.

CONTRAINDICATIONS

MYQORZO is contraindicated with concomitant use of rifampin.

WARNING AND PRECAUTIONS

Heart Failure
MYQORZO reduces cardiac contractility, which can reduce LVEF and cause heart failure.

Patients who experience a serious intercurrent illness (eg, serious infection) or arrhythmia (eg, new or uncontrolled atrial fibrillation) may be at greater risk of developing systolic dysfunction and heart failure.

Assess patients’ clinical status and LVEF prior to and during treatment and adjust the MYQORZO dose accordingly. New or worsening arrhythmia, dyspnea, chest pain, fatigue, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide may be signs and symptoms of heart failure.

Initiation of MYQORZO in patients with LVEF <55% is not recommended.

MYQORZO REMS Program

MYQORZO is available only through a restricted program called the MYQORZO REMS Program, because of the risk of heart failure due to systolic dysfunction.

Notable requirements of the MYQORZO REMS Program include:

  • Prescribers must be certified by enrolling in the MYQORZO REMS Program
  • Patients must enroll in the MYQORZO REMS Program and comply with ongoing monitoring requirements
  • Pharmacies must be certified by enrolling in the MYQORZO REMS Program and must only dispense to patients who are authorized to receive MYQORZO
  • Wholesalers and distributors must only distribute to certified pharmacies

Further information is available at www.MYQORZOREMS.com, or at 1-844-285-7367.

Cytochrome P450 Interactions Leading to Heart Failure or Loss of Effectiveness
MYQORZO is metabolized primarily by CYP2C9, and to a lesser extent by CYP3A, CYP2D6, and CYP2C19 enzymes. Initiation of medications that inhibit multiple P450 pathways of MYQORZO elimination (eg, fluconazole, voriconazole, or fluvoxamine) or strong CYP2C9 inhibitors, and discontinuation of moderate-to-strong CYP3A inducers may lead to increased blood concentrations of aficamten and increase the risk of heart failure due to systolic dysfunction. Conversely, initiation of medications that induce P450 pathways of MYQORZO (eg, rifampin, moderate-to-strong CYP3A inducers) may lead to decreased blood concentrations of aficamten and potential loss of effectiveness. Assess LVEF 2 to 8 weeks after initiation of such inhibitors or after discontinuation of such inducers and adjust the dose of MYQORZO accordingly.

Advise patients of the potential for drug interactions. Advise patients to inform their healthcare provider of all concomitant medications prior to and during MYQORZO treatment.

ADVERSE REACTIONS

Hypertension (8% vs 2%) was the only adverse reaction occurring in >5% of patients and more commonly on MYQORZO than on placebo in the pivotal trial.

INDICATIONS AND USAGE

MYQORZO is indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms.

Please see full Prescribing Information, including Boxed WARNING.