Acoramidis Shows 34% Lower Hazard of Composite Clinical Worsening Than Tafamidis in Real-World ATTR-CM Study

BridgeBio Pharma reported on September 23, 2026, that acoramidis was associated with a 34% lower hazard of composite clinical worsening than tafamidis in a retrospective, real-world study of patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Published in Cardiology and Therapy, the analysis found a lower hazard of diuretic intensification with acoramidis, although the individual differences in heart failure hospitalization and mortality were not statistically significant.

ATTR-CM and the Comparative Treatment Question

ATTR-CM is a progressive condition in which transthyretin (TTR) forms amyloid deposits in the heart muscle, contributing to heart failure. It can arise from inherited TTR variants or age-related changes in wild-type TTR. Acoramidis and tafamidis stabilize TTR to reduce protein misfolding and amyloid formation.

Both treatments are approved for ATTR-CM, but randomized head-to-head trials have not established their comparative effectiveness. This study addresses that evidence gap using real-world clinical outcomes rather than comparing treatment effects against placebo.

Study Design and Patient Population

Researchers used US claims data from the Komodo Healthcare Map linked with Claritas hub and specialty pharmacy data. The retrospective, longitudinal, new-user, active-comparator study evaluated patients initiating acoramidis or tafamidis between December 11, 2024, and April 30, 2025, with follow-up through July 31, 2025.

After propensity score weighting, the analysis included 170 acoramidis-treated patients and a weighted sample size of 448 tafamidis-treated patients. Mean follow-up was 139 days with acoramidis and 143 days with tafamidis, approximately 4.6 and 4.7 months, respectively.

The primary outcome was diuretic intensification, defined by initiation or escalation of diuretic treatment. The secondary composite comprised diuretic intensification, heart failure-related hospitalization, and mortality. Baseline heart failure therapy was broadly balanced, including sodium-glucose cotransporter-2 inhibitors and mineralocorticoid receptor antagonists.

Clinical Results: Diuretic Intensification Drives the Signal

Acoramidis was associated with a 43% lower hazard of diuretic intensification than tafamidis (11.8% versus 20.5%; HR 0.57; 95% CI 0.35–0.92; p=0.021). For initiation or dose escalation of oral loop diuretics, the corresponding rates were 10.0% versus 18.9% (HR 0.52; 95% CI 0.31–0.87; p=0.014).

The composite clinical worsening outcome occurred in 17.6% of acoramidis-treated patients and 26.4% of tafamidis-treated patients. This corresponded to a 34% lower hazard with acoramidis (HR 0.66; 95% CI 0.44–0.99; p=0.046).

However, the individual component outcomes require a more cautious interpretation. Heart failure hospitalization occurred in 10.6% versus 12.3% of patients (HR 0.90; 95% CI 0.53–1.55; p=0.71), while mortality occurred in 1.2% versus 2.3% (HR 0.52; 95% CI 0.11–2.42; p=0.41), respectively. Neither difference was statistically significant.

The composite result therefore supports an association with fewer combined clinical worsening events, but it does not establish that acoramidis independently reduces hospitalization or mortality compared with tafamidis.

Clinical Interpretation of the Findings

The separation of cumulative-incidence curves within weeks of treatment initiation, which remained divergent during follow-up, is consistent with an early difference in observed outcomes. However, the short observation period does not establish whether this difference persists over the longer term.

Diuretic intensification is a clinically relevant marker of worsening heart failure and is associated with adverse outcomes. Nevertheless, treatment escalation can also depend on clinician decisions and patient-specific factors. The findings therefore suggest a potential difference in early disease stability, rather than proving superior disease modification.

Eight acoramidis-treated patients (4.6%) and 54 tafamidis-treated patients (7.7%) switched treatments during follow-up. This descriptive difference should not be interpreted as proof of better tolerability or treatment persistence.

 Clinical Development and Regulatory Implications

Acoramidis is approved in the United States as Attruby for adults with wild-type or variant ATTR-CM to reduce cardiovascular death and cardiovascular-related hospitalization. The comparative study does not alter the approved indication or establish a new treatment recommendation.

Its limitations include residual confounding, incomplete capture of disease severity measures such as cardiac biomarkers and functional status, lack of independent adjudication of cardiac events, and follow-up of less than eight months. Although the study’s falsification analyses were non-significant, these results cannot exclude residual bias. BridgeBio has also reported plans to present additional real-world comparative data using electronic health records.

Overall, the study provides an early real-world signal favoring acoramidis for diuretic intensification and a composite clinical outcome. Longer follow-up and independent comparative evidence are needed to determine whether these associations translate into meaningful differences in hospitalization, survival, and sustained clinical outcomes.

Reference

Acoramidis Associated with Significantly Improved Clinical Outcomes Versus Tafamidis in ATTR-CM in an Independent, Real-World Study of U.S. Electronic Health Records, BridgeBio Pharma, 11 October 2026

Comparative Effectiveness of TTR Stabilizers for the Treatment of ATTR-CM Using Real-World Evidence. Cardiology and Therapy. 2026.