Abstract Background The National Amyloidosis Centre (NAC) staging system for transthyretin amyloid cardiomyopathy (ATTR-CM) is used to classify patients into prognostic categories based on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and estimated glomerular filtration rate (eGFR). The NAC staging system has been shown to predict ongoing survival throughout the course of ATTR-CM, with survival progressively decreasing from stage I to stage III. Acoramidis, a highly selective, oral transthyretin stabilizer that achieves near-complete (≥90%) transthyretin stabilization, has recently been approved in Europe and the USA for the treatment of wild-type or variant ATTR-CM in adults. In the phase 3 ATTRibute-CM study, acoramidis treatment was well tolerated and led to a 42% relative risk reduction in the composite of all-cause mortality and recurrent cardiovascular hospitalizations over 30 months compared with placebo (p=0.0005). Purpose To evaluate the ability of acoramidis treatment, as compared with placebo, to stabilize or improve NAC stage after 30 months in participants with ATTR-CM from the ATTRibute-CM study. Methods Participants in ATTRibute-CM were randomized 2:1 to receive acoramidis or placebo for 30 months. Efficacy analyses were conducted in the modified intention-to-treat population, which consisted of all randomized participants who had received at least one dose of acoramidis or placebo, had at least one efficacy evaluation after baseline and had a baseline eGFR ≥30 mL/min/1.73 m2. NAC stage at baseline and Month 30 was assessed. Changes from baseline to Month 30 were categorized as "stable", "improved" or "worsened". The "stable" category comprised participants who stayed within the same NAC stage at baseline and Month 30. The "improved" category comprised participants who moved from a higher NAC stage at baseline to a lower stage at Month 30. The "worsened or missing" category comprised participants who moved from a lower NAC stage at baseline to a higher stage at Month 30 and participants whose Month 30 NAC stage was missing. The change in NAC stage was compared between treatment groups using a stratified Cochran-Mantel-Haenszel test with stratification factors of genotype, NT-proBNP level and eGFR as recorded in the interactive voice/web response system at randomization. Results Overall, 611 participants were analysed (acoramidis: n=409; placebo: n=202). Baseline characteristics were comparable between treatment groups. Most participants had NAC stage I at baseline (acoramidis: 58.9%; placebo: 59.4%; Table). At Month 30, NAC stage remained stable or improved in 52.1% of acoramidis participants compared with 43.1% of placebo participants (p=0.0351; Figure). Conclusions Acoramidis treatment resulted in a greater proportion of participants whose NAC stage improved or remained stable at Month 30 compared with placebo, indicating better stabilization of their disease.
Gillmore et al. (Sat,) studied this question.
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