Acoramidis Shows Durable Benefit at 54 Months in ATTR-CM

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, often fatal condition driven by misfolded transthyretin (TTR) protein deposits in the heart muscle. Acoramidis (Attruby; BridgeBio Pharma), a near-complete oral TTR stabilizer approved for ATTR-CM, demonstrated significant clinical benefits through 30 months in the phase 3 ATTRibute-CM trial.¹ Now, an open-label extension (OLE) of that trial reports that those benefits are not only sustained but amplified with continued early treatment through 54 months of follow-up.

Published in JAMA Cardiology, the OLE enrolled 389 patients with ATTR-CM who completed the 30-month ATTRibute-CM trial between October 2021 and April 2025. Patients who had received acoramidis during the trial continued treatment (continuous acoramidis group), while those who had received placebo were switched to acoramidis at OLE entry (delayed initiation group).

Early Treatment Advantage Grows Over Time

The central finding of the OLE is that the survival advantage conferred by early, uninterrupted acoramidis treatment widened with longer follow-up. Through month 54, the continuous acoramidis group showed incremental reductions in all-cause mortality, cardiovascular-related mortality, and first cardiovascular hospitalization compared with the delayed initiation group.

“These findings support the importance of early and continuous long-term treatment with acoramidis in transthyretin amyloid cardiomyopathy,” wrote the study authors.

The benefit-of-early-treatment signal is clinically significant: Patients who spent 30 months on placebo before crossing over to acoramidis never fully closed the gap with those who started treatment at trial enrollment. This suggests that disease progression occurring during delayed treatment may not be fully reversible, reinforcing the importance of prompt diagnosis and initiation of therapy.

Mechanism and Clinical Context

Acoramidis works by stabilizing the TTR tetramer, preventing its dissociation into the monomers that misfold and aggregate as amyloid fibrils in cardiac tissue. At the regimen used in ATTRibute-CM, acoramidis achieves greater than 90% TTR stabilization, a higher degree of stabilization than tafamidis, the other approved oral TTR stabilizer.

These findings have translated into consistent clinical outcomes. An earlier analysis from the ATTRibute-CM program found that acoramidis demonstrated significant reductions in the composite of all-cause mortality or first cardiovascular hospitalization evident within 3 months and sustained through 30 months in both wild-type and variant ATTR-CM.²

Safety Profile Remains Favorable

The OLE reported no clinically important new safety concerns through 54 months. The drug was generally well tolerated, and treatment discontinuations were low.¹ These long-term safety data are particularly meaningful given that ATTR-CM is a chronic, progressive disease requiring indefinite therapy.

Patient Population and Study Design

The OLE was a multicenter, open-label study. Patients who had received concomitant tafamidis during ATTRibute-CM were required to discontinue it before enrolling in the OLE, ensuring a clean comparison between continuous and delayed acoramidis exposure. The study population was representative of the broader ATTR-CM clinical landscape, predominantly older adults with symptomatic heart failure, many of whom had either wild-type or variant (hereditary) disease.

Implications for Practice

The OLE results reinforce a clear clinical message: in ATTR-CM, earlier treatment initiation with acoramidis yields better long-term outcomes than delayed therapy. The data demonstrate that early initiation resulted in sustained incremental reductions in all-cause mortality, cardiovascular-related mortality, and first cardiovascular hospitalization through month 54.

For cardiologists managing ATTR-CM, these findings support proactive screening and early treatment initiation, particularly in older patients presenting with unexplained heart failure, thickened ventricular walls, or low-voltage electrocardiogram patterns. The 54-month data set now provides one of the longest follow-up periods available for any approved ATTR-CM therapy, offering meaningful reassurance about both efficacy durability and safety.

References

1. Soman P, Cuddy SAM, Gillmore JD, et al. Long-term durability of acoramidis efficacy in transthyretin amyloid cardiomyopathy: open-label extension of the ATTRibute-CM randomized clinical trial. JAMA Cardiol. 2026;11(5):446-454. doi:10.1001/jamacardio.2026.0819
2. Alexander KM, Davis MK, Akinboboye O, et al. Efficacy of acoramidis in wild-type and variant transthyretin amyloid cardiomyopathy: results from ATTRibute-CM and its open-label extension. JAMA Cardiol. 2026;11(1):57-67. doi:10.1001/jamacardio.2025.4477