Experts' Perspectives: Advancements in Cardiomyopathy at ACC.24

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A trio of experts discuss their perspectives on the recent advancement in pharmacotherapy within the management of hypertrophic cardiomyopathy.

In recent years, advancements in the treatment of cardiomyopathies have captivated the cardiology. However, experts and opinion leaders in cardiomyopathy are quick to remind others this progress was not overnight and comes as the result of tireless efforts by colleagues and their predecessors dating back decades.

In the last decade, a greater understanding of pathophysiology has given way to numerous advances in management, including the introduction of cardiac myosin inhibitors into treatment algorithms of patients with obstructive hypertrophic cardiomyopathy, such as mavacamten (Camzyos), which received approval for obstructive hypertrophic cardiomyopathy in April 2022. Now, the community looks ahead with anticipation to phase 3 data for a next-generation cardiac myosin inhibitor in aficamten.

At the American College of Cardiology 2024 (ACC.24) Annual Scientific Sessions, investigators presented data from the 1-year cohort of FOREST-HCM, which is an ongoing open-label extension study. In the presentation, investigators detailed the results of the first 45 patients to achieve 1-year of follow-up.

Upon analysis, results indicated use of aficamten was associated with a complete hemodynamic response in 91% of patients and more than 80% of patients experienced and maintained an improvement of 1 or more New York Heart Association class improvement during the 1 year of follow-up. Analysis of drug safety suggested there was 1 temporary dose interruption at 8 weeks, 1 dose reduction at 48 weeks, and no drug discontinuations due to LVEF decline.

If this were not enough, the field was given hope for a potential treatment for the management of nonobstructive hypertrophic cardiomyopathy with the results of the IMPROVE-HCM trial, which examined use of the cardiac mitotrope ninerafaxstat. Presented at ACC.24, results of the trial indicate use of ninerafaxstat was associated with was associated with a non-significant LS mean difference of 3.1 between the groups (P=.2) for change in KCCQ-CSS from baseline to the end of the treatment period, with a greater proportion of patients receiving ninerafaxstat achieving an improvement in KCCQ-CSS of 5 or more, 10 or more, or 20 or more points.

For more perspective on the advancement events in cardiomyopathy, check out our interview with key opinion leaders Sara Saberi, MD, Martin Maron, MD, and Ahmad Masri, MD.

Relevant disclosures for Saberi include Cytokinetics and Bristol-Myers Squibb Company. Relevant disclosures for Maron include Imbria, Cytokinetics, Edgewise, and iRhythm. Relevant disclosures for Masri include Cytokinetics, Bristol Myers Squibb, Eidos, Pfizer, Ionis, Lexicon, AstraZeneca, Tenaya, and others.

References:

  1. Bristol Myers Squibb. U.S. Food and Drug Administration approves CamzyosTM (Mavacamten) for the treatment of adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms. Bristol Myers Squibb. April 28, 2022. Accessed April 10, 2024. https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-Camzyos-mavacamten-for-the-Treatment-of-Adults-With-Symptomatic-New-York-Heart-Association-Class-II-III-ObstructiveHypertrophic-Cardiomyopathy-HCM-to-Improve-Functional-Capacity-and-Symptoms/default.aspx.
  2. Saberi S, Abraham TP, Choudhury L, et al, Hutchinson HG, Wolski K et al. EFFICACY AND SAFETY OF AFICAMTEN IN THE FIRST COHORT OF PATIENTS WITH SYMPTOMATIC OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY COMPLETING 1-YEAR FOLLOW-UP: FINDINGS FROM THE FOREST-HCM STUDY. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
  3. Maron MS, Mahmod Masliza, Abd Samat AH, et al. Safety and Efficacy of Metabolic Modulation with Ninerafaxstat in Nonobstructive Hypertrophic Cardiomyopathy: Phase 2 Study. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
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