Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease associated with a significant burden of recurrent cardiovascular (CV) events. A new post hoc analysis of the ATTRibute-CM trial suggests that acoramidis, an oral transthyretin (TTR) stabiliser, significantly reduces the cumulative burden of these outcomes.¹

Methodology

This exploratory analysis used data from the phase 3, randomised, double-blind ATTRibute-CM trial and its open-label extension (OLE).¹˒² The modified intention-to-treat population included 611 participants with ATTR-CM (acoramidis, n=409; placebo, n=202) who received either acoramidis hydrochloride 800mg or a matching placebo twice daily for 30 months.

The analysis assessed the cumulative incidence of centrally adjudicated CV-related mortality (CVM) and recurrent CV-related hospitalisation (CVH), including urgent heart failure visits, through to month 30, with further follow-up to month 42 in the OLE.¹

Results

Treatment with acoramidis was associated with a significant reduction in the cumulative risk of CVM or recurrent CVH through month 30 compared with placebo (HR: 0.51; 95% CI: 0.43–0.62; p<0.0001). Numerically fewer cumulative events were observed in the acoramidis group by month 1, and this difference increased progressively over the study period. By month 30, this translated to 53 events avoided per 100 treated participants.¹

The benefit was observed across both components of the composite endpoint. The annualized frequency of recurrent CVH was significantly decreased through month 30 (relative risk ratio: 0.50; 95% CI: 0.35–0.69; p<0.0001). In the OLE, continuous treatment with acoramidis was associated with a lower risk of CVM through month 42 compared with participants who switched from placebo to acoramidis (HR: 0.55; 95% CI: 0.39–0.79; p=0.0011).¹

The analysis also highlighted the early burden of the disease, with 22% of all CVH events and 19% of all CVM or recurrent CVH events occurring within the first 6 months of the trial.¹

In Practice

These findings build on previous reports from the ATTRibute-CM trial, which demonstrated the efficacy of acoramidis on all-cause mortality and first CVH.² This new analysis, focusing on the total burden of events, suggests that the benefits of treatment may appear early and are sustained. The high rate of CV events in the first 6 months underscores the time-sensitive nature of ATTR-CM. The study authors suggest that these exploratory findings highlight the importance of timely evaluation, diagnosis, and treatment initiation to potentially alter the disease trajectory.¹ Data collection is ongoing in the OLE of the ATTRibute-CM trial.

This study was funded by BridgeBio Pharma, Inc.

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References

1. Masri A, Judge DP, Ruberg FL, et al. Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis From ATTRibute-CM. J Am Coll Cardiol. 2026;87(5):490-501. https://doi.org/10.1016/j.jacc.2025.09.013

2. Gillmore JD, Judge DP, Cappelli F, et al. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med. 2024;390:132-142. https://doi.org/10.1056/NEJMoa2305434