Early Increase in Serum Transthyretin by Acoramidis for Enhanced Survival in TTR Amyloid Cardiomyopathy
Maurer M. S., et al. Journal of the American College of Cardiology, 2025, 85(20), 1911-1923.
In the ATTRibute-CM Phase 3 study, acoramidis, a novel high-affinity transthyretin (TTR) stabilizer, was assessed for its impact on serum transthyretin (sTTR) levels and all-cause mortality (ACM) in 557 patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Participants received acoramidis treatment, leading to a rapid and significant elevation in sTTR levels (mean increase of 9.1 mg/dL) within 28 days, which was maintained over 30 months. Kaplan-Meier survival analyses and Cox modeling identified early ΔTTR (day 28) as an independent predictor of reduced ACM (HR: 0.96 per 1 mg/dL; 95% CI: 0.93-0.98; P = 0.002). Multivariate adjustment for baseline clinical variables, including New York Heart Association functional class and TTR variant status, confirmed early ΔTTR as a robust prognostic marker (P < 0.001). Mediation analyses revealed that early ΔTTR fully mediated the treatment effect of acoramidis on ACM reduction (average causal mediation effect = -0.117; P = 0.002). Logistic regression further demonstrated a 31.6% relative reduction in ACM odds per 5 mg/dL sTTR increment. These findings substantiate the application of acoramidis in stabilizing TTR and improving survival outcomes in ATTR-CM, with early ΔTTR serving as a key pharmacodynamic marker of therapeutic efficacy.
