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15-01-2024 | Cardiomyopathy | Editor's Choice | News

ATTRibute-CM data support acoramidis use in TTR amyloid cardiomyopathy

Author: Laura Cowen

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medwireNews: Treatment with the high-affinity transthyretin (TTR) stabilizer acoramidis may improve mortality, morbidity, and function relative to placebo in patients with TTR amyloid cardiomyopathy, suggest data from the phase 3 ATTRibute-CM trial.

Acoramidis, also called AG-10, is a novel agent that inhibits “dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo,” explain Julian Gilmore (University College London, UK) and co-investigators.

“As compared with other well-characterized TTR stabilizers (tafamidis, diflunisal, and tolcapone), acoramidis has shown improved potency, binding affinity, binding-site occupancy, binding thermodynamics, and TTR stabilization when assayed by a number of quantitative techniques,” they add.

In the current study, Gilmore and team randomly assigned 611 patients (mean age 77 years, 90% men) with TTR amyloid cardiomyopathy to receive acoramidis hydrochloride 800 mg twice daily (n=409) or placebo (n=202) for 30 months.

They compared the two treatment arms using a four-step primary hierarchical analysis, which included death from any cause, cardiovascular-related hospitalization, change from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, and change from baseline in 6-minute walk distance.

This method is useful because “all possible paired comparisons are made only at the initial step (i.e., death from any cause in this trial),” the researchers remark. “At each subsequent step, only those ties remaining after the previous step are subject to a paired comparison.”

The analysis showed that patients given acoramidis had a better outcome 1.8 times more often than those given placebo when pairwise comparisons were carried out within each strata of TTR genotype (wild-type or variant), NT-proBNP level (≤3000 or >3000 pg/mL), and estimated glomerular filtration rate (<45 or ≥45 mL/min per 1.73 m2).

Specifically, 63.7% of pairwise comparisons favored acoramidis and 35.9% favored placebo.

Among the individual outcomes, NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3 vs 7.0%), but death from any cause and cardiovascular-related hospitalization together made the greatest contribution to the win ratio, with 58% of comparisons determined once these first two hierarchical components had been considered.

The investigators also calculated that individuals given acoramidis were 50% less likely to be hospitalized for cardiovascular reasons per year than those given placebo.

Most patients in both the acoramidis and placebo arms experienced at least one adverse event (AE; 98.1% and 97.6%, respectively), whereas serious AEs were less common with acoramidis than with placebo (54.6% and 64.9%).

Writing in The New England Journal of Medicine, Gilmore and co-authors conclude: “These data support the use of acoramidis as an effective and safe treatment option for patients with transthyretin amyloid cardiomyopathy.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

N Engl J Med 2024; 390: 132–142

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