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The following is a summary of “Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy,” published in the March 2025 issue of Journal of the American College of Cardiology by Judge et al.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and underdiagnosed disease characterized by worsening heart failure, diminished quality of life, recurrent hospitalizations, and premature mortality. Acoramidis, a selective oral transthyretin stabilizer, has recently been approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM, offering a promising therapeutic option for affected individuals. In phase 3, randomized, double-blind ATTRibute-CM trial, acoramidis demonstrated favorable clinical efficacy and safety, significantly improving the primary composite endpoint encompassing all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, and 6-minute walk distance. 

This study aimed to characterize further the impact of acoramidis on ACM and CVH outcomes. A total of 632 participants with ATTR-CM were randomized in a 2:1 ratio to receive either acoramidis hydrochloride (800 mg twice daily) or a placebo for 30 months. The primary efficacy analyses included 611 participants with baseline estimated glomerular filtration rate ≥30 mL/min/1.73 m², assessed using Kaplan-Meier survival estimates and stratified Cox proportional hazards modeling. The study demonstrated a significant reduction in the composite of ACM or first CVH in the acoramidis group (35.9%) compared to placebo (50.5%) (HR: 0.64; 95% CI: 0.50-0.83; P = 0.0008), with divergence in Kaplan-Meier curves evident as early as month 3 and continuing throughout the study period. Additionally, acoramidis reduced the occurrence of first CVH (26.7% vs. 42.6%; HR: 0.60; 95% CI: 0.45-0.80; P = 0.0005) and significantly decreased the annualized frequency of CVH compared to placebo (0.22 vs. 0.45; relative risk ratio: 50%; 95% CI: 0.36-0.70; P < 0.0001). These benefits were consistent across subgroups, reinforcing the broad applicability of acoramidis in ATTR-CM management. Importantly, acoramidis was well tolerated, with no emerging safety concerns of clinical significance. 

These findings establish acoramidis as an effective therapeutic option that not only reduces cardiovascular-related hospitalizations but may also provide early and sustained benefits in disease progression. The results highlight the potential of acoramidis to redefine the treatment landscape for ATTR-CM, underscoring its role in improving long-term patient outcomes through early and sustained disease-modifying effects.

Source: sciencedirect.com/science/article/pii/S0735109724105566