Acoramidis Achieves Long-Term Disease Stabilization in People with Transthyretin Amyloid Cardiomyopathy

Continuous use of transthyretin (TTR) stabilizer acoramidis reduced the risk of all-cause mortality and cardiovascular disease-related mortality and achieved durable disease stabilization in individuals with transthyretin amyloid cardiomyopathy (ATTR-CM) who continued treatment up to 54 months, according to long-term data from the ATTRibute-CM study. 
 
ATTR-CM is a progressive cardiac condition that results from the accumulation of wild type or variant amyloid fibrils in the myocardium. Patients living with this disease often experience progressive symptoms, including worsening heart failure and arrhythmias, which lead to hospitalizations, impaired health-related quality of life, and a reduced life expectancy. While there is currently no cure for ATTR-CM, multiple therapies that can alter disease progression have been developed over the past decade. ATTR-CM-specific therapies now include acoramidis, a highly selective oral TTR stabilizer that achieves near-complete (≥90%) TTR stabilization, which is approved in the United States, Europe, Japan, Switzerland, and the United Kingdom for the treatment of variant or wild-type ATTR-CM in adults.

In the phase 3 ATTRibute-CM study, which enrolled more than 600 patients who were randomized to receive acoramidis hydrochloride at a dose of 800 mg or matching placebo twice daily for 30 months, treatment with acoramidis reduced the risk of all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) compared with placebo through month 30, with clinical benefits becoming apparent as early as 3 months after treatment initiation (Gillmore JD et al. N Engl J Med 2024; 390:132-142). Moreover, acoramidis achieved ATTR-CM disease stabilization, reflected in sustained increases in serum TTR concentrations and stabilized N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. In the primary analysis, the overall incidence of adverse events emerging during treatment was comparable between the acoramidis group and the placebo group (98.1% and 97.6%, respectively).
 
The latest data from the open-label extension phase, presented at the 2026 Annual Meeting of the American Association of Heart Failure Nurses (AAHFN 2026) in San Diego, California, reinforced the previous safety and efficacy results, showing that clinical benefits were sustained long-term in individuals who continued treatment with acoramidis in the open-label extension phase of the trial. Of nearly 400 participants who chose to participate in the open-label extension phase, 263 individuals continued treatment with acoramidis and 126 people switched from placebo to acoramidis. 

The long-term analysis, which was conducted after all participants completed at least 24 months in the open-label extension phase (unless they had discontinued early), showed that continuous acoramidis treatment led to a risk reduction of 45% in ACM and of 49% in cardiovascular disease-related mortality (CVM) compared to the switch from placebo to acoramidis, indicating a durable benefit that was sustained through month 54. ACM was defined as death from any cause, heart transplantation, or receipt of an implanted cardiac mechanical assist device, while CVM was defined as any death adjudicated as cardiovascular. 

“When looking at people who were on acoramidis for the first time [in the open-label extension phase], it is no surprise that they did not show benefit immediately,” said lead author Nancy Albert, PhD, APRN-CCNS, a clinical nurse specialist at Cleveland Clinic’s Linda H. Kaufman Center for Heart Failure Treatment and Recovery, who presented the long-term data at AAHFN 2026. “In the early open-label phase, the trajectory of benefit did not show improvement immediately after being switched to acoramidis. However, similar to the first 30 months of study, after approximately 16 to 18 months, we started to see the decrease in mortality risk, reinforcing that, once the 4-unit tetramers stabilize, the benefit continues over time.”

The long-term survival benefit associated with continuous acoramidis treatment appeared consistent across different demographic subgroups, with no evidence of heterogeneity in treatment effect based on age, sex, race, or other key factors. Treatment was well tolerated through month 54, reinforcing the role of acoramidis as a long-term ATTR-CM-specific therapy. 

“Participants in the placebo-to-acoramidis group had more advanced disease than those in the continuous acoramidis group,” Albert noted. “The goal is to start therapy early, when someone is diagnosed, get them on the right medication, and keep them on the medication long-term - unless there is a need to switch to a silencer or another stabilizer. Silencers and stabilizers work well, so, providers should pick whichever one is the best fit for their patients.” Albert stressed that adherence and continuation of therapy play a crucial role in slowing down disease progression. 

Data presented at AAHFN 2026 also showed that treatment with acoramidis achieved durable disease stabilization in patients with variant ATTR-CM, who tend to experience earlier onset of the disease and increased clinical severity. Among the randomized participants with variant ATTR-CM, acoramidis treatment was associated with a notably smaller median change from baseline in NT-proBNP levels compared with placebo at all time points, from month 3 to month 30. While the NT-proBNP levels were comparable between the placebo and treatment groups of participants with variant ATTR-CM at baseline, acoramidis treatment mitigated the rise in this biomarker, a tendency that remained consistent through month 54. 

“This is significant because, when you think about the ATTR-CM variant population, their disease progresses much more rapidly, so they have a higher incidence of mortality and morbidity and increased hospitalizations,” said presenting author Elizabeth Hushka, MSN, a nurse practitioner at the University of Chicago Medical Center. “So, the fact that this [therapy] harnesses this critical biomarker for variant [ATTR-CM] so well has translated to the clinical data, where we saw a reduction in mortality rates [in this group].” 

The authors noted that the long-term data support the early initiation of acoramidis and the continuation of therapy to achieve durable disease stabilization in both variant and wild type ATTR-CM.