Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy

REDWOOD-HCM Steering Committee and Investigators

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients.

OBJECTIVES: This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM.

METHODS: Patients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout.

RESULTS: From baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: -40 ± 27 mm Hg, and -43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (-36 ± 27 mm Hg and -53 ± 44 mm Hg, P = 0.001 and <0.0001 vs placebo, respectively). There were modest reductions in EF (-6% ± 7.5% and -12% ± 5.9%, P = 0.007 and P < 0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro-B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms.

CONCLUSIONS: Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM.

Original languageEnglish (US)
Pages (from-to)34-45
Number of pages12
JournalJournal of the American College of Cardiology
Issue number1
StatePublished - Jan 3 2023


  • aficamten
  • clinical trial
  • hypertrophic cardiomyopathy
  • obstructive hypertrophic cardiomyopathy
  • therapy
  • Cardiomyopathy, Hypertrophic/complications
  • Humans
  • Ventricular Outflow Obstruction
  • Heart Failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy'. Together they form a unique fingerprint.

Cite this