Aficamten Shows Promise in Difficult to Treat Non-Obstructive Hypertrophic Cardiomyopathy


Data from cohort 4 in REDWOOD-HCM provides the first insight into the effects of aficamten in a cohort of patients with non-obstructive hypertrophic cardiomyopathy.

New data from the REDWOOD-HCM study presented at the American College of Cardiology’s (ACC) 2023 Annual Scientific Session Together With the World Congress of Cardiology suggests use of aficamten was associated with significant improvements in symptoms and cardiac biomarkers in patients with non-obstructive hypertrophic cardiomyopathy (HCM).

A difficult to treat population with few management options, Cytokinetics noted the new data pertaining to non-obstructive HCM, which was obtained from the phase 2 trial’s cohort 4, support advancement of the agent’s development towards a phase 3 trial.

“Patients with non-obstructive HCM have no effective medical therapies and lack an apparent therapeutic target like reducing or eliminating the LVOT obstruction, underscoring the need for a therapy to address the underlying cause of the disease,” said Fady Malik, MD, PhD, executive vice president of Research & Development at Cytokinetics.2 “The results from Cohort 4 of REDWOOD-HCM demonstrate that treatment with aficamten is well-tolerated and associated with significant improvements in heart failure symptoms and cardiac biomarkers in patients with non-obstructive HCM and support the advancement of aficamten into a pivotal Phase 3 clinical trial in patients with non-obstructive HCM.”

A phase 2, multi-center, randomized, placebo-controlled, double-blind, dose finding clinical trial of aficamten, the REDWOOD-HCM trial included 4 cohorts, with cohorts 1, 2, and 3 enrolling patients with obstructive HCM and cohort 4 enrolling patients with non-obstructive HCM.1

A total of 41 patients were enrolled in cohort 4, with all these patients being classified as New York Heart Association (NYHA) Class II or III with left ventricular ejection fraction (LVEF) of 60% or greater without a resting or provoked left ventricle outflow tract (LVOT) gradient. Further inclusion criteria required patients to have an NT-proBNP equal to or greater than 300 pg/mL and no history of an LVEF of less than 45%.1

Per trial protocol, all patients received aficamten at a beginning dose of 5 mg once daily, which was increased to 10 and 15 mg based on LVEF. Trial participants participated in visits at baseline and weeks 2, 4, 6, 10, and 12, with the total treatment duration lasting 10 weeks and the final 2 weeks serving as a washout period.1

Upon analysis, results from cohort 4 indicated use of aficamten was associated with significant improvements in NT-proBNP, which decreased by a mean of 66% (P <.0001) and hs-cTnI levels, which decreased significantly at each study visit (P <.05). Investigators pointed out both NT-proBNP and hs-cTnI levels returned to baseline levels following the 2-week washout period. Additionally, an improvement of at least 1 NYHA functional class was observed among 54% of patients in the cohort, with 2 patients improving from NYHA class III to NYHA class I.1

Investigators pointed out 85% of cohort 4 achieved a 15 mg dose of aficamten during the study and there were no drug discontinuations due to adverse events.1

At ACC 2023, HCPLive sat down with study presenter Ahmad Masri, MD, director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, to learn more about the effects of aficamten in non-obstructive HCM.


  2. Cytokinetics presents positive results from Cohort 4 of redwood-HCM and long-term results from Forest-HCM at the American College of Cardiology 72nd annual Scientific Session. Cytokinetics, Inc. Published March 4, 2023. Accessed March 6, 2023.

Masri has received consultant fees or research grants from Cytokinetics, Akcea, Alnylam, Attralus, Bristol-Myers Squibb, and others. Here is a full list of disclosures.

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