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Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy

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Abstract

Aficamten is a novel cardiac myosin inhibitor that has demonstrated its ability to safely lower left ventricular outflow tract (LVOT) gradients and improve heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM). Based on the REDWOOD-HCM open label extension (OLE) study, participants receiving aficamten had significantly reduced resting and Valsalva LVOT gradient within 2 weeks after initiating treatment, with ongoing improvements over 24 weeks, and recent evidence suggests effects can sustain up to 48 weeks. While beta-blockers, calcium channel blockers, and disopyramide have shown some benefits in managing HCM, they have limited direct impact on the underlying disease process in patients with obstructive HCM. Aficamten achieves its therapeutic effect by reducing hypercontractility and improving diastolic function in obstructive HCM. Mavacamten was the first cardiac myosin inhibitor approved for symptomatic obstructive HCM. However, aficamten has a shorter human half-life (t1/2) and fewer drug–drug interactions, making it a preferable treatment option. This review evaluates the long-term clinical value and safety of aficamten in patients with obstructive HCM based on available data from completed and ongoing clinical trials. Additionally, the molecular basis of sarcomere-targeted therapy in reducing LVOT gradients is explored, and its potential in managing obstructive HCM is discussed.

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Authors and Affiliations

  1. Department of Internal Medicine, Azeezia Medical College, Kollam, Kerala, India

    Sneha Annie Sebastian

  2. Department of Internal Medicine, Richmond University Medical Center/Mount Sinai, Staten Island, NY, USA

    Inderbir Padda

  3. Division of Cardiac Surgery, Swedish Heart and Vascular Institute, Seattle, WA, USA

    Eric J. Lehr

  4. Department of Cardiology, University of Washington, Valley Medical Center, Seattle, WA, USA

    Gurpreet Johal

  5. Airdrie, Canada

    Sneha Annie Sebastian

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Correspondence to Sneha Annie Sebastian.

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The authors Sneha Annie Sebastian, Inderbir Padda, Eric J Lehr, and Gurpreet Johal declare that we have no conflict of interest. Also, the authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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SAS: conceptualization, methodology, investigation, data curation, writing—original draft, writing—review and editing. IP: writing—original draft. EJL: writing—review and editing. GJ: writing—review and editing.

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Sebastian, S.A., Padda, I., Lehr, E.J. et al. Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy. Am J Cardiovasc Drugs 23, 519–532 (2023). https://doi.org/10.1007/s40256-023-00599-0

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