Acoramidis reduced the risk of first outpatient worsening heart failure by 41% compared to placebo in patients with transthyretin amyloid cardiomyopathy (HR 0.59; 95% CI 0.46-0.75).
RCT (n=611)
Does acoramidis reduce outpatient worsening heart failure and improve clinical outcomes in patients with transthyretin amyloid cardiomyopathy?
In patients with ATTR-CM, acoramidis significantly reduces the risk of outpatient worsening heart failure compared to placebo, an event that is strongly associated with increased mortality and cardiovascular hospitalization.
Hazard Ratio: 0.59 (95% CI 0.46–0.75)
BACKGROUND: Acoramidis, an oral transthyretin stabilizer that achieves near-complete (≥90%) transthyretin stabilization, demonstrated significant clinical benefit over placebo in participants with transthyretin amyloid cardiomyopathy (ATTR-CM) in the phase 3 ATTRibute-CM trial (NCT03860935). METHODS: Post-hoc exploratory analyses of ATTRibute-CM were performed to evaluate associations between outpatient worsening heart failure (HF) (initiation/escalation of oral loop diuretics) and clinical outcomes, the impact of acoramidis on outpatient worsening HF, and the effect of acoramidis on clinical outcomes adjusting for time-dependent first outpatient worsening HF. RESULTS: In the modified-intention-to-treat population, 287/611 participants (46.97%) experienced outpatient worsening HF, which was associated with an increased risk of all-cause mortality (ACM)/recurrent cardiovascular hospitalization (CVH) (hazard ratio HR 1.95, 95% confidence interval CI 1.51-2.51), first CVH (HR 2.78, 95% CI 1.95-3.95), ACM (HR 1.64, 95% CI 1.14-2.36), and cardiovascular mortality (HR 1.63, 95% CI 1.08-2.46) through month 30. Acoramidis was associated with a 41% risk reduction of first outpatient worsening HF versus placebo (HR 0.59, 95% CI 0.46-0.75); Kaplan-Meier curves separated early, nominal statistical significance was first reached at day 30 (HR 0.562, 95% CI 0.317-0.998; p = 0.0492), and sustained nominal statistical significance was achieved at day 134 through month 30. When adjusting for time-dependent first outpatient worsening HF over 30 months, acoramidis reduced the risk of ACM/recurrent CVH and first CVH versus placebo. CONCLUSIONS: Outpatient worsening HF was associated with clinical outcomes in ATTR-CM. Acoramidis reduced the risk of outpatient worsening HF; effects emerged early and persisted throughout follow-up.
“New analyses suggest Attruby (acoramidis) may reduce the risk of outpatient worsening heart failure, with differences seen within 30 days and sustained through 30 months in adults with transthyretin amyloid cardiomyopathy (ATTR-CM). The analyses were based on data from the large Phase 3 ATTRibute-CM (NCT03860935) trial. In a company press release, Bridgebio, the therapy's developer, said the findings suggest Attruby exhibits “the fastest time to impact of any disease modifying treatment in ATTR-CM.””
Fontana et al. (Thu,) conducted a rct in transthyretin amyloid cardiomyopathy (ATTR-CM) (n=611). Acoramidis vs. placebo was evaluated on First outpatient worsening heart failure (HR 0.59, 95% CI 0.46-0.75). Acoramidis reduced the risk of first outpatient worsening heart failure by 41% compared to placebo in patients with transthyretin amyloid cardiomyopathy (HR 0.59; 95% CI 0.46-0.75).