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Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy

Sneha Annie Sebastian1,2, Inderbir Padda3, Eric J Lehr4

  • 1Department of Internal Medicine, Azeezia Medical College, Kollam, Kerala, India. snehaann1991@gmail.com.

American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions
|August 1, 2023
PubMed

Insights

Aficamten, a novel cardiac myosin inhibitor, effectively reduces left ventricular outflow tract gradients and improves heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM). This treatment shows sustained efficacy and a favorable safety profile in long-term studies.

Area of Science:

  • Cardiology
  • Pharmacology
  • Genetics

Background:

  • Obstructive hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease characterized by abnormal thickening of the heart muscle, leading to left ventricular outflow tract (LVOT) obstruction and heart failure symptoms.
  • Current treatments like beta-blockers, calcium channel blockers, and disopyramide offer symptomatic relief but do not directly address the underlying hypercontractility in obstructive HCM.
  • Aficamten represents a new class of therapeutics, cardiac myosin inhibitors, designed to target the molecular basis of HCM by reducing cardiac muscle hypercontractility.

Purpose of the Study:

  • To evaluate the long-term clinical efficacy and safety of aficamten in patients with obstructive hypertrophic cardiomyopathy (HCM).
  • To explore the molecular mechanisms of sarcomere-targeted therapy in reducing LVOT gradients.
  • To discuss the potential of aficamten as a preferred treatment option compared to existing therapies and other myosin inhibitors.

Main Methods:

  • Analysis of data from the REDWOOD-HCM open-label extension (OLE) study and other ongoing clinical trials.
  • Assessment of changes in resting and Valsalva left ventricular outflow tract (LVOT) gradients.
  • Evaluation of heart failure symptom improvement and safety profiles, including adverse events and drug-drug interactions.

Main Results:

  • Aficamten significantly reduced resting and Valsalva LVOT gradients within two weeks of treatment initiation.
  • Sustained improvements in LVOT gradients were observed up to 48 weeks in patients receiving aficamten.
  • Aficamten demonstrated a favorable safety profile and was associated with improvements in heart failure symptoms.

Conclusions:

  • Aficamten is a safe and effective treatment for reducing LVOT gradients and improving symptoms in obstructive HCM.
  • Its shorter half-life and reduced potential for drug-drug interactions make it a potentially preferable option compared to mavacamten.
  • Sarcomere-targeted therapy with aficamten offers a promising approach for managing obstructive HCM by addressing the underlying pathophysiology.

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