Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM (SEQUOIA-HCM)

A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of CK-3773274 in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction

The purpose of this study is to evaluate the efficacy and safety of aficamten (CK-3773274) versus placebo in adults with symptomatic hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract obstruction.

Study Overview

• Status: Completed
• Conditions: Obstructive Hypertrophic Cardiomyopathy (oHCM)
• Intervention / Treatment: Drug: Aficamten (5 mg, 10 mg, 15 mg, and 20 mg); Drug: Placebo to match aficamten

Detailed Description

CY 6031 was a Phase 3, randomized, placebo-controlled, double-blind, multi-center trial in participants with symptomatic oHCM. Eligible participants were randomized in a 1:1 ratio to receive aficamten or placebo. Randomization was stratified by use of beta-blockers (yes or no) and cardiopulmonary exercise testing (CPET) exercise modality (treadmill or bicycle). Enrollment limits were applied as follows: participants taking beta-blockers were capped at approximately 70% of total enrollment; participants taking disopyramide were capped at approximately 10% of total enrollment; participants with persistent atrial fibrillation (AF) at screening were capped at approximately 15% of total enrollment; and participants using the bicycle CPET exercise modality were capped at approximately 50% of total enrollment.

Investigational product (IP) was administered orally once daily (QD) with or without food for 24 weeks. During the initial 6 weeks of the treatment period, IP doses were individually titrated at Weeks 2, 4, and 6 based on echocardiography-guided criteria. Dose escalation at Weeks 2, 4, and 6 occurred only if a participant had a Valsalva left ventricular outflow tract gradient (LVOT-G) ≥ 30 mmHg and a biplane left ventricular ejection fraction (LVEF) ≥ 55%. Echocardiograms were performed at each subsequent visit during the trial, and the IP dose was down-titrated if the LVEF was < 50%. The primary endpoint of peak oxygen uptake (pVO2) was measured by CPET at screening and at the end of treatment (Week 24). A participant's background HCM therapy was individually optimized according to local practice prior to enrollment in the study.

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100020
      • Beijing Chao-Yang Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China, 100029
      • Beijing Anzhen Hospital
    • Beijing, Beijing Municipality, China, 10019
      • Peking University Third Hospital
  • Guangdong
    • Guanzhou, Guangdong, China, 516006
      • Nanfang Hospital Southern Medical University
  • Henan
    • Zhengzhou, Henan, China, 450018
      • the First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of the Central South University
  • Jinlin
    • Changchun, Jinlin, China, 130031
      • The First Hospital of Jinlin University
  • Shanxi
    • Xi’an, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
• Czechia
  • Prague, Czechia, 128 08
    • Charles University
  • Prague, Czechia, 12808
    • Interni klinika kardiologie a angiologie
• Denmark
  • Aalborg, Denmark, 9100
    • Aalborg University Hospital, Department of Cardiology
  • Aarhus, Denmark, 8200
    • Department of Cardiology Aarhus University Hospital
  • Copenhagen, Denmark, 2400
    • Copenhagen University Hospital
  • Copenhagen, Denmark, 2100
    • Hjertecentret (The Heart Center)
• France
  • Marseille, France, 13005
    • CHU de Marseille - Hopital de la Timone Service de cardiologie
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75010
    • Hopital Lariboisiere, Service de Cardiologie
  • Paris, France
    • CHU Pitie-Salpetriere, Centre de reference maladies cardiaques hereditaires ou rares
  • Pessac, France, 33600
    • CHU de Bordeaux Hopital Cardiologique Haut-Leveque
  • Pessac, France, 33604
    • CHU du Haut Lveque Cardiologie
  • Cedex
    • Toulouse, Cedex, France, 31059
      • Hopital Universitaire de Rangueil (CHU de Toulouse) Service de Cardiologie
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik GmbH Abteilung Administration Forschung und Lehre
  • Berlin, Germany, 13353
    • Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum (CVK) Medizinische Klinik mit Schwerpunkt Kardiologie
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen Westdeutsches Herz-Gefaesszentrum
  • Göttingen, Germany, 37075
    • Klinikumder Georg-August-Universitaet
  • Göttingen, Germany, 37075
    • Universitaetsmedizin Goettingen
  • Heidelberg, Germany
    • Universitaetsklinikum Heidelberg
  • Jena, Germany, 07747
    • Universitaetsklinikum Jena Klinik fuer Innere Medizin 1
  • Magdeburg, Germany, 39120
    • Unniversitaetsklinikum Magdeburg Klinik fur Kardiologie und Anglologie
  • Würzburg, Germany
    • Universitatsklinikum Wurzburg
• Hungary
  • Budapest, Hungary
    • Semmelweis Egyetem Varosmajori Sziv es Ergyogyasazati Klinika
• Israel
  • Ashkelon, Israel, 7830604
    • The Barzilai University Medical Center
  • Ashkelon, Israel, 78100
    • The Barzilai University Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center- Ein Kerem
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Safed, Israel, 13100
    • Ziv Medical Center
  • Tel Hasomer
    • Ramat Gan, Tel Hasomer, Israel, 5265601
      • The Olga & Lev Leviev Heart Center The Chaim Sheba Medical Center
• Italy
  • Brescia, Italy, 25123
    • UOC Cardiologica Azienda Ospedaliera Spedali Civili di Brescia
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi Dipartimento Cardiotoracovascolare - Cardiomiopatie Unit
  • Pisa, Italy, 56124
    • Fondazione toscana Gabriele Monesterio per la ricarca medica Dipartimento Cardiotoracico UOC Cardiologia e Medicina Cardiovasculare Ospedale San Cataldo
  • Roma, Italy, 1035-39
    • Dipartimento di Medicina Clinica e Molecolare Universita Sapienza di Roma Unita di Terapia Intensiva Cardiologica Azienda Ospedaliero Universitaria Sant'Andrea
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Amsterdam UMC, location AMC
  • Maastricht, Netherlands, 6229HX
    • University Hospital Maastricht
  • Rotterdam, Netherlands, 3015
    • Erasmus Medical Center
• Poland
  • Katowice, Poland
    • Kardio Brynow S.C
  • Krakow, Poland
    • Krakowskie Centrum
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 04-628
      • Narodowy Instytut Kardiologii Stefana Kardynała Wyszynskiego- Panstwowy Instytut Badawczy
• Portugal
  • Aveiro, Portugal, 3814-501
    • Centro Hospitalar Do Baixo Vouga, EPE AV ARTUR RAVARA
  • Lisbon, Portugal, 1500-650
    • Hospital da Luz
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Murcia, Spain
    • Hospital Clínico Universitario Virgen de la Arrixaca
  • Palma, Spain, 07198
    • Hospital Universitario Son Llatzer Secretaria de Cardiologia
  • Salamanca, Spain, 37007
    • Hospital Universitario De Salamanca
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena-merge
  • La Coruna
    • A Coruña, La Coruna, Spain, 15006
      • Complejo Hospitalario Universitario
  • Majadahonda
    • Madrid, Majadahonda, Spain
      • Hospital Universitario Puerta de Hierro
• United Kingdom
  • Glasgow, United Kingdom, G1 4TF
    • Queen Elizabeth University Hospital - HWS Greater Glasgow and Clyde
  • Liverpool, United Kingdom, L14 3LB
    • Liverpool Heart and Chest Hospital - Liverpool Heart and Chest Hospital NHS Foundation Trust- HWS Greater Glasgow and Clyde
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • London, United Kingdom, SW17 0QT
    • St George's University Hospitals NHS Foundation Trust
  • London, United Kingdom, EC1A 7BE
    • Barts Health NS Trust
  • Oxford, United Kingdom, OX3 9DU
    • Oxford Centre for Clinical Magnetic Resonance Research
  • Oxford, United Kingdom, OX3 9DU
    • Radcliffe Department of Medicine
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2GW
      • Queen Elizabeth Hospital Birmingham University Hospitals Birmingham NHS Foundation Trust
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Heart and Vascular Institute
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Health - Sulpizio Cardiovascular Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center - Smidt Heart Institute Clinic
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
    • New Haven, Connecticut, United States, 06511
      • Yale School of Medicine
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital / Cardiology Associates
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
    • Fayetteville, Georgia, United States, 30214
      • Piedmont Fayette Hospital
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Franklin Square Medical Center
    • Baltimore, Maryland, United States, 21218
      • MedStar Medical Group Cardiology at Union Memorial
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center
    • Grand Rapids, Michigan, United States, 49525
      • Spectrum Health Medical Group Cardiovascular Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview University of Minnesota Medical Center - East Bank
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center/NY Presbyterian Hospital
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 10595
      • Sanger Heart and Vascular Institute
    • Charlotte, North Carolina, United States, 28204
      • Sanger Heart and Vascular Institute - HCM Clinic
    • Morrisville, North Carolina, United States, 27560
      • Duke Health Center Arringdon
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Ascension St. John Clinical Research Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation, Inc
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System University Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 cardiac disease and

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

    • ≥15 mm in one or more myocardial segments OR
    • ≥13 mm in one or more wall segments and a known-disease-causing gene mutation or positive family history of HCM
• Has resting LVOT-G ≥30 mmHg and post-Valsalva LVOT G ≥50 mmHg during screening as determined by the echocardiography core laboratory.
• LVEF ≥60% at screening as determined by the echocardiography core laboratory.
• New York Heart Association (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 CPET per the core laboratory.
• Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for >6 weeks prior to randomization and anticipate remaining on the same medication regimen during the trial. Patients treated with disopyramide must also be concomitantly treated with a beta blocker and/or calcium channel blocker.

Key Exclusion Criteria:

• Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy 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 the mitral valve.
• History of LV systolic dysfunction (LVEF <45%) or stress cardiomyopathy at any time during their clinical course.
• Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations).
• Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol 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, atrial fibrillation 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 months prior to screening.
• History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
• Has received prior treatment with CK-3773274 or mavacamten.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aficamten up to 20 mg; Participants received 5 mg, 10 mg, 15 mg, or 20 mg of aficamten; dose levels were guided by echocardiography assessments. Treatment was administered for up to 24 weeks.	Drug: Aficamten (5 mg, 10 mg, 15 mg, and 20 mg); Aficamten tablets were administered orally once daily.; Other Names: CK-3773274
Placebo Comparator: Placebo to match aficamten; Participants received placebo for up to 24 weeks.	Drug: Placebo to match aficamten; Placebo tablets were administered orally once daily.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in pVO2 at Week 24	The effect of CK-3773274 on exercise capacity in participants with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) was determined through changes in peak oxygen uptake (pVO2) after 24 weeks of treatment. pVO2 was measured by cardiopulmonary exercise testing (CPET) on a treadmill or bicycle. A higher pVO2 indicates better cardiorespiratory fitness.	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in KCCQ-CSS at Week 24	The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social limitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.	Baseline to Week 24
Change From Baseline in KCCQ-CSS at Week 12	The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social limitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.	Baseline to Week 12
Proportion of Participants With ≥1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 24	The effect of aficamten on NYHA functional classification was evaluated through changes observed from baseline through 24 weeks of treatment.	Baseline to Week 24
Proportion of Participants With ≥1 Class Improvement in NYHA Functional Class From Baseline to Week 12	The effect of aficamten on NYHA functional classification was evaluated through changes observed from baseline through 12 weeks of treatment.	Baseline to Week 12
Change From Baseline in Valsalva Left Ventricular Outflow Tract Gradient (LVOT-G) at Week 24	The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 24.	Baseline to Week 24
Change From Baseline in Valsalva LVOT-G at Week 12	The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.	Baseline to Week 12
Proportion of Participants With Valsalva LVOT G <30 mmHg at Week 24	The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 24.	Baseline to Week 24
Proportion of Participants With Valsalva LVOT G <30 mmHg at Week 12	The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.	Baseline to Week 12
Duration of SRT Eligibility During the 24-week Treatment Period for Participants Who Were SRT Eligible at Baseline	The effect of aficamten treatment on the duration of septal reduction therapy (SRT) eligibility was evaluated over the 24- week treatment period.	Baseline to Week 24
Change From Baseline to Week 24 in Total Workload During CPET	Effect of aficamten on intensity of exercise (based on speed, incline, participant weight, etc.) during CPET. Workload is an indication of the energy expended during the exercise test.	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Cytokinetics
• Collaborators: Corxel Pharmaceuticals
• Investigators: Study Director: Cytokinetics MD, Cytokinetics

Publications and helpful links

General Publications

• Kaski JP, Kantor PF, Nakano SJ, Olivotto I, Russell MW, Godown J, Chiu M, German P, Heitner SB, Jacoby DL, Kupfer S, Lutz J, Maharao N, Malik FI, Melloni C, Nieto Morales PF, Simkins T, Wei J, Ho CY; CEDAR-HCM Investigators. Efficacy and Safety of Aficamten in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy: Study Design and Rationale of CEDAR-HCM. Circ Heart Fail. 2026 Feb;19(2):e013418. doi: 10.1161/CIRCHEARTFAILURE.125.013418. Epub 2025 Dec 5.
• Campain J, Griskowitz C, Newlands C, Claggett BL, Kulac IJ, McGinnis S, Giverts I, Moreno F, Minasian A, Prasad C, Rupert L, Landsteiner I, Iskenderian N, Coats CJ, Lee MMY, Maron MS, Owens AT, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Wohltman A, Malhotra R, Lewis GD. Characterization and Application of Novel Exercise Recovery Patterns That Reflect Cardiac Performance: A Substudy of the SEQUOIA-HCM Trial. Circulation. 2025 Oct 7;152(14):990-1002. doi: 10.1161/CIRCULATIONAHA.124.073585. Epub 2025 Sep 5.
• Maron MS, Masri A, Nassif ME, Barriales-Villa R, Abraham TP, Arad M, Cardim N, Choudhury L, Claggett B, Coats CJ, Dungen HD, Garcia-Pavia P, Hagege AA, Januzzi JL, Kulac I, Lee MMY, Lewis GD, Ma CS, Michels M, Oreziak A, Owens AT, Spertus JA, Solomon SD, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins HC, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Olivotto I; SEQUOIA-HCM Investigators. Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Coll Cardiol. 2024 Nov 5;84(19):1821-1831. doi: 10.1016/j.jacc.2024.09.003. Epub 2024 Sep 30.
• Lee MMY, Masri A, Nassif ME, Barriales-Villa R, Abraham TP, Claggett BL, Coats CJ, Gimeno JR, Kulac IJ, Landsteiner I, Ma C, Maron MS, Olivotto I, Owens AT, Solomon SD, Veselka J, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Lewis GD; SEQUOIA-HCM Investigators. Aficamten and Cardiopulmonary Exercise Test Performance: A Substudy of the SEQUOIA-HCM Randomized Clinical Trial. JAMA Cardiol. 2024 Nov 1;9(11):990-1000. doi: 10.1001/jamacardio.2024.2781.
• Sherrod CF 4th, Saberi S, Nassif ME, Claggett BL, Coats CJ, Garcia-Pavia P, Januzzi JL, Lewis GD, Ma C, Maron MS, Miao ZM, Olivotto I, Veselka J, Butzner M, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Spertus JA. Effect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Coll Cardiol. 2024 Nov 5;84(19):1773-1785. doi: 10.1016/j.jacc.2024.08.014. Epub 2024 Sep 1.
• Masri A, Cardoso RN, Abraham TP, Claggett BL, Coats CJ, Hegde SM, Kulac IJ, Lee MMY, Maron MS, Merkely B, Michels M, Olivotto I, Oreziak A, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Solomon SD, Wohltman A, Kwong RY, Kramer CM; SEQUOIA-HCM Investigators. Effect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM CMR Substudy. J Am Coll Cardiol. 2024 Nov 5;84(19):1806-1817. doi: 10.1016/j.jacc.2024.08.015. Epub 2024 Sep 1.
• Hegde SM, Claggett BL, Wang X, Jering K, Prasad N, Roshanali F, Masri A, Nassif ME, Barriales-Villa R, Abraham TP, Cardim N, Coats CJ, Kramer CM, Maron MS, Michels M, Olivotto I, Saberi S, Jacoby DL, Heitner SB, Kupfer S, Meng L, Wohltman A, Malik FI, Solomon SD; SEQUOIA-HCM Investigators. Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2024 Nov 5;84(19):1789-1802. doi: 10.1016/j.jacc.2024.08.002. Epub 2024 Sep 1.
• Coats CJ, Masri A, Nassif ME, Barriales-Villa R, Arad M, Cardim N, Choudhury L, Claggett B, Dungen HD, Garcia-Pavia P, Hagege AA, Januzzi JL, Lee MMY, Lewis GD, Ma CS, Maron MS, Miao ZM, Michels M, Olivotto I, Oreziak A, Owens AT, Spertus JA, Solomon SD, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins H, Jacoby DL, German P, Heitner SB, Kupfer S, Lutz JD, Malik FI, Meng L, Wohltman A, Abraham TP; SEQUOIA-HCM Investigators *. Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Heart Assoc. 2024 Aug 6;13(15):e035993. doi: 10.1161/JAHA.124.035993. Epub 2024 Jul 26.
• Maron MS, Masri A, Nassif ME, Barriales-Villa R, Arad M, Cardim N, Choudhury L, Claggett B, Coats CJ, Dungen HD, Garcia-Pavia P, Hagege AA, Januzzi JL, Lee MMY, Lewis GD, Ma CS, Michels M, Olivotto I, Oreziak A, Owens AT, Spertus JA, Solomon SD, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins H, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Abraham TP; SEQUOIA-HCM Investigators. Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. 2024 May 30;390(20):1849-1861. doi: 10.1056/NEJMoa2401424. Epub 2024 May 13.
• Coats CJ, Maron MS, Abraham TP, Olivotto I, Lee MMY, Arad M, Cardim N, Ma CS, Choudhury L, Dungen HD, Garcia-Pavia P, Hagege AA, Lewis GD, Michels M, Oreziak A, Owens AT, Tfelt-Hansen J, Veselka J, Watkins HC, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Meng L, Wohltman A, Masri A; SEQUOIA-HCM Investigators. Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design. JACC Heart Fail. 2024 Jan;12(1):199-215. doi: 10.1016/j.jchf.2023.10.004. Epub 2023 Nov 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): November 10, 2023
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Obstructive Hypertrophic Cardiomyopathy; oHCM; CK-3773274; CK-274; Aficamten; SEQUOIA-HCM; CY 6031; SEQUOIA
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Cardiomyopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: CY 6031; 2021-003536-92 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No