Key result
Acoramidis improves LV systolic function in ~54% of patients vs 20% on placebo.
Why the study?
The proportion of patients with ATTR-CM achieving long-term improvement in cardiac structure and function on acoramidis through Month 30 and an open-label extension at Month 42, contextualized against a natural history cohort, needed evaluation.
Does long-term acoramidis improve cardiac structure and function on CMR at 30 and 42 months compared with placebo and a natural history cohort in patients with transthyretin amyloid cardiomyopathy?
RCT (n=52)
Blinded outcome assessment with open-label extension
Yes
Does long-term acoramidis improve cardiac structure and function on CMR at 30 and 42 months compared with placebo and a natural history cohort in patients with transthyretin amyloid cardiomyopathy?
Long-term treatment with acoramidis over 30 to 42 months resulted in clinically meaningful improvements in LV systolic function in approximately one-third of ATTR-CM patients and reduced indexed LV mass in 46% of patients at 42 months, exceeding improvement rates seen with placebo and natural history.
Acoramidis-linked CMR gains in ATTR-CM warrant outcome validation; extends stabilization data but remains hypothesis-generating.
Background In ATTR-CM, progressive myocardial dysfunction from transthyretin (TTR) destabilization can lead to heart failure with preserved ejection fraction. Acoramidis, an approved oral TTR stabilizer, achieves near-complete (≥90%) TTR stabilization. In the cardiac magnetic resonance imaging (CMR) substudy of the ATTRibute-CM study, acoramidis trended to improving or stabilizing myocardial CMR parameters including left ventricular (LV) ejection fraction (LVEF), indexed LV stroke volume (LVSVi) and indexed LV mass (LVMi) vs placebo from initial CMR to Month (M) 30. Three acoramidis recipients (13%) had improved extracellular volume. Increases of 5% in LVEF and 5 mL in LVSV at M18 have been associated with all-cause mortality reductions of 15% and 23%, respectively. Purpose To evaluate the proportion of participants (pts) with improved cardiac structure and function at M30 and M42 in the ATTRibute-CM CMR substudy and its ongoing open-label extension (OLE), respectively and to contextualize results with a natural history cohort at M24. Methods Eligible ATTRibute-CM pts were enrolled in the CMR substudy from 2 UK sites. After the initial CMR, pts had scans at predefined timepoints including at M30 and in the OLE at M42. CMR was blinded to all other clinical data and analysed at the National Amyloidosis Centre. The proportions of pts with ‘improved’ CMR parameters were assessed for LVEF (absolute change from baseline [CFB] ≥5%), LVSVi (CFB ≥5 mL/m2), LVMi (CFB ≤−5 g/m2) and LV systolic function (improvement in LVEF or LVSVi, with the other parameter not worsening). Completer and conservative analyses were performed; the former included a natural history cohort. Results Of the 52 pts (male, n=47; mean age, 74.3 years) in the CMR substudy, 31 (acoramidis, n=26; placebo, n=5) completed scans at M30 and 19 of 33 in the continuous acoramidis group at M42. Baseline characteristics (n=52, mean: LVEF=50.6%; LVSVi=38.4 mL/m2; LVMi=118.8 g/m2) were comparable in the 2 groups. Acoramidis showed favourable trends vs placebo in CMR parameters at M30 and M42. Completer analysis showed improved LV systolic function in 54% (14/26) of acoramidis recipients by M30 (vs 20% [1/5] with placebo) and in 53% (10/19) of continuous acoramidis recipients by M42 (Table 1). In the natural history cohort, 26% (11/42) of completers had improved function at M24. Conservative analysis showed improved function in 34% (14/41) of acoramidis recipients by M30 (vs 9% [1/11] with placebo) and in 30% (10/33) of continuous acoramidis recipients by M42; LVMi improved in 46% (15/33) of pts at M42 (Table 2). Conclusions Long-term acoramidis treatment showed clinically meaningful LV systolic function improvement in ~1/3 of pts with ATTR-CM over 30–42 months, and LVMi reduction in 46% of pts at M42. Improvement rates with acoramidis exceeded placebo starting at M30, suggesting alteration of the expected disease trajectory. Larger confirmatory studies are needed.
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Sheikh et al. (2026) conducted an RCT in Transthyretin amyloid cardiomyopathy (ATTR-CM) (n=52). Acoramidis vs. Placebo (and contextualized with a natural history cohort) was evaluated on Improved LV systolic function (improvement in LVEF ≥5% or LVSVi ≥5 mL/m2, with the other parameter not worsening) at Month 30. Acoramidis improved LV systolic function in 54% vs 20% of placebo patients at 30 months (completer analysis; 34% vs 9% conservative) and reduced LVMi in 46% at 42 months.
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