The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to aficamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy.

Aficamten is an investigational oral, selective, small molecule cardiac myosin inhibitor designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle, thereby suppressing the myocardial hypercontractility associated with hypertrophic cardiomyopathy.

The designation was based on data from cohorts 1 and 2 of the multicenter, randomized, double-blind, placebo-controlled phase 2 REDWOOD-HCM trial (ClinicalTrials.gov Identifier: NCT04219826), which evaluated aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy. Patients were randomly assigned to receive oral tablets of aficamten 5mg to 15mg (cohort 1), 10mg to 30mg (cohort 2) or placebo for 10 weeks.

Results showed that treatment with aficamten was associated with statistically significant reductions from baseline in the average resting left ventricular outflow tract pressure gradient (LVOT-G) and the average post-Valsalva LVOT-G, compared with placebo. Moreover, 78.6% and 92.9% of patients in cohorts 1 and 2, respectively, achieved the target goal of treatment, defined as resting gradient less than 30mmHg and post-Valsalva gradient less than 50mmHg at week 10 compared with 7.7% of patients in the placebo arm. Patients in the aficamten arm also had improvements in heart failure symptoms and reductions in NT-proBNP.

“The results of REDWOOD-HCM met our high expectations supporting the potential role of aficamten as an innovative therapy to address the hypercontractility that underlies oHCM,” said Fady I. Malik, MD, PhD, Cytokinetics’ Executive Vice President of Research & Development. “With start-up activities underway in SEQUOIA-HCM, our phase 3 clinical trial of aficamten, we look forward to its further development and engaging with FDA as may hopefully benefit patients whose lives are severely impacted by this disease.”

References

  1. Cytokinetics announces receipt of Breakthrough Therapy Designation from FDA for aficamten. News release. Cytokinetics, Inc. Accessed December 9, 2021. https://www.globenewswire.com/news-release/2021/12/09/2349098/35409/en/Cytokinetics-Announces-Receipt-of-Breakthrough-Therapy-Designation-from-FDA-for-Aficamten.html
  2. Pipeline: Aficamten. Cytokinetics, Inc. Accessed December 9, 2021. https://cytokinetics.com/aficamten/.