USA: In the phase III ACACIA-HCM trial involving 517 patients with symptomatic nonobstructive hypertrophic cardiomyopathy (HCM), treatment with aficamten (Myqorzo) significantly improved both exercise capacity and health status compared with placebo. The double-blind, placebo-controlled study met both dual primary endpoints, showing improvements from baseline to week 36 in peak oxygen uptake (VO₂) and the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).

The findings, presented at the European Society of Cardiology annual meeting and published simultaneously in the New England Journal of Medicine, suggest that aficamten may provide meaningful functional and symptomatic benefits in patients with symptomatic nonobstructive HCM.
The study was conducted by Ahmad Masri, M.D., Oregon Health and Science University, Portland, and colleagues. The investigators highlighted that nonobstructive HCM is a relatively common cardiac disorder that can cause substantial symptoms and morbidity. Unlike obstructive HCM, where established treatment approaches are available for some patients, there is currently no proven medical therapy specifically demonstrated to improve outcomes in symptomatic nonobstructive disease.
Aficamten is a selective cardiac myosin inhibitor designed to reduce excessive actin-myosin interactions and improve cardiac muscle function. The researchers evaluated whether targeting cardiac hypercontractility with aficamten could translate into measurable improvements in functional capacity and patients’ perceived health status.
The multinational phase III trial enrolled adults with symptomatic nonobstructive HCM and randomly assigned them in a 1:1 ratio to receive either aficamten or placebo. Treatment was initiated at 5 mg, with dose adjustments permitted up to a maximum of 20 mg. Participants were followed for as long as 72 weeks.
The trial had two primary endpoints assessed at week 36. The first was the change in peak oxygen uptake, an objective measure of aerobic exercise capacity. The second was the change in the KCCQ-CSS, which assesses patients’ symptoms, physical limitations, social limitations and quality of life. Scores range from 0 to 100, with higher scores indicating better health status.
Among the 517 participants, 258 received aficamten, and 259 received placebo. The mean age of the study population was 55.1 years, and 53.6% were women, providing representation of both men and women with symptomatic nonobstructive HCM.
The key findings were as follows:
  • At week 36, KCCQ-CSS improved by 11.4 points with aficamten versus 8.4 points with placebo (between-group difference, 3.0 points).
  • Peak oxygen uptake increased by 0.64 mL/kg/min with aficamten, compared with a 0.03 mL/kg/min decline with placebo (between-group difference, 0.67 mL/kg/min).
  • Reversible reductions in left ventricular ejection fraction below 50% occurred in 10.5% of patients receiving aficamten versus 0.8% with placebo.
  • Serious adverse events were reported in 20.2% of aficamten-treated patients and 14.7% of placebo-treated patients.
Overall, the ACACIA-HCM findings indicate that aficamten was associated with statistically significant improvements in both exercise capacity and patient-reported health status among patients with symptomatic nonobstructive HCM. The results provide clinical evidence supporting cardiac myosin inhibition as a potential therapeutic strategy for a patient population that has historically had limited targeted treatment options.
Reference:
DOI: 10.1056/NEJMoa2603021


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Article Source : New England Journal of Medicine

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Medha Baranwal

Medha Baranwal holds a Bachelor’s degree in Biomedical Sciences from the University of Delhi and a Master’s degree in Biotechnology from Amity University. Since May 2018, she has been contributing to Medical Dialogues, writing and editing medical news articles that translate complex research into clear, accessible information for healthcare professionals.

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