Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy.

Summary

In the phase 3 ATTRibute-CM RCT (n=611 in modified ITT), acoramidis reduced the composite of all-cause mortality or first cardiovascular hospitalization vs placebo (35.9% vs 50.5%; HR 0.64, 95% CI 0.50–0.83) and first CVH alone (26.7% vs 42.6%; HR 0.60). Event curves separated by month 3 and continued to diverge through 30 months. Tolerability was favorable with no new safety signals.

Key Findings

• Reduced ACM or first CVH with acoramidis vs placebo (HR 0.64; 95% CI 0.50–0.83).
• Reduced first CVH alone (HR 0.60; 95% CI 0.45–0.80), with curves separating by month 3.
• Lower annualized CVH frequency with acoramidis (0.22 vs 0.45; relative risk ratio ~50%).
• Benefit consistent across clinical subgroups; no new safety signals.

Clinical Implications

Acoramidis can be considered for patients with ATTR-CM to reduce early and sustained risk of CV hospitalization and mortality. Early initiation may be advantageous given the early separation of event curves. Monitoring aligns with routine amyloidosis care; no new safety concerns emerged.

Limitations

• Early benefit driven largely by reduction in CV hospitalizations; mortality effects over longer-term require continued evaluation.
• Trial inclusion criteria may limit generalizability to very advanced or comorbid populations.

Future Directions

Head-to-head comparisons with other TTR stabilizers/silencers, real-world effectiveness in diverse populations, and mechanistic biomarker substudies to refine patient selection.