Effects of Acoramidis on Kidney Function in Transthyretin Amyloid Cardiomyopathy.

Authors

Jeffrey M Testani, Daniel P Judge, Barry A Borlaug, David Cherney, Zachary L Cox, Julian D Gillmore, Julia B Lewis, Scott H Adler, Xiaofan Cao, Adam Castaño, Jonathan C Fox, Leonid Katz, Vandana Mathur, Kuangnan Xiong, Javed Butler, Ahmad Masri

Published in

Circulation. Heart failure. Pages e014656. Jul 02, 2026. Epub Jul 02, 2026.

Abstract

Acoramidis achieves near-complete (≥90%) transthyretin stabilization and is approved to reduce cardiovascular-related hospitalization in transthyretin amyloid cardiomyopathy. Its effects on kidney function are not well characterized.
Data from randomized phase 2 (N=49) and phase 3 (N=632) studies in transthyretin amyloid cardiomyopathy were included. The estimated glomerular filtration rate (eGFR) slope was generated using a linear spline mixed-effects model. The urinary albumin-to-creatinine ratio was measured longitudinally. Relationships between changes in kidney function and clinical outcomes were explored using Cox proportional hazards models.
Acoramidis initiation resulted in a modest acute dip in eGFR that was dose-dependent, reversible, and not associated with adverse kidney-related events. At Day 28, the mean (±SE) dip in eGFR from baseline with acoramidis was 8.5±0.48 mL/min per 1.73 m²; the placebo-corrected reduction in the urinary albumin-to-creatinine ratio was 15.5% (95% CI, 0.4%-28.4%; P=0.044). The rate of decline in kidney function (chronic eGFR slope) was significantly improved with acoramidis versus placebo (-1.01 versus -3.48 mL/min per 1.73 m² per year; P<0.001), and the reduction in the urinary albumin-to-creatinine ratio was sustained (13.7% [95% CI, 1.7%-24.2%]; P=0.026) over time. Concomitant tafamidis use did not influence the chronic eGFR slope in either arm. Comparing acoramidis versus placebo subgroups with acute eGFR dips ≥ the median (4.89 mL/min per 1.73 m²) favored acoramidis for all-cause mortality or cardiovascular-related hospitalization (hazard ratio, 0.42 [95% CI, 0.22-0.78]; P=0.006; P interaction=0.043) and cardiovascular-related hospitalization (hazard ratio, 0.34 [95% CI, 0.17-0.66]; P=0.002, P interaction=0.025). Within the placebo arm, eGFR dips portended worse outcomes.
Acoramidis initiation resulted in an acute dip in eGFR and reductions in both the chronic eGFR slope and urinary albumin-to-creatinine ratio versus placebo without adverse kidney-related events. Acoramidis effects on kidney function may be mediated through direct kidney-protective hemodynamic effects. Importantly, the acute dip in eGFR was associated with a reduced risk of adverse clinical outcomes within the first year.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03458130. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03536767. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03860935. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04988386.

PMID:
42389794
Bibliographic data and abstract were imported from PubMed on 02 Jul 2026.

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