ATTRibute-CM: Acoramidis Lowers Mortality in Patients With Amyloid Cardiomyopathy

Acoramidis has shown its efficacy in reducing all-cause mortality (ACM) in patients with amyloid cardiomyopathy (ATTR-CM) with both wild-type (ATTRwt-CM) and a pathogenic variant (ATTRv-CM), which was consistent out to month 42 of the ATTRibute-CM study’s open-label extension.1

These data were presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, in a series of moderated and unmoderated digital posters. The results are consistent with previously presented results from the ATTRibute-CM study in the wild-type population, as well as in the population overall.1

“These data represent an important finding for patients with the V142I variant of ATTR-CM, a population that has historically had limited access to early diagnosis and treatment,” Kevin Alexander, MD, Stanford University School of Medicine, said in a statement. “These results are encouraging for individuals with variant ATTR-CM and reflect progress in advancing precision medicine and promoting equity in cardiovascular care.”1

ATTRibute-CM was a phase 3, randomized, double-blind, 30-month study comparing acoramidis 712 mg and matching placebo. Patients were randomly assigned in a 2:1 ratio to either treatment delivered daily for 30 months, which would be followed by 12 months of open-label treatment. Patient stratification was based on TTR genotype, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels, and estimated glomerular filtration rate (eGFR) levels. During the study, patients were allowed to initiate tafamidis at the discretion of the investigator as a concomitant medication, once they had completed 12 months of treatment.2

A total of 632 participants were initially enrolled; 611 of these were included in a modified intent-to-treat (mITT) population. Of these, 9.7% (n = 59) exhibited ATTRv-CM at randomization; the other 552 had ATTRwt-CM. Ultimately, 39 participants were assigned to acoramidis and 20 to placebo. Efficacy outcomes of the trial included all-cause mortality, cardiovascular-related hospitalizations, serum TTR, 6-minute walk distance, and NT-pro-BNP.2

Investigators saw consistent efficacy in both ATTRv-CM and ATTRwt-CM for both all-cause mortality and cardiovascular-related hospitalizations through month 30, and in all-cause mortality through month 42. By month 30, acoramidis reduced the risk of both versus placebo by 31% in ATTRwt-CM (HR, 0.69; 95% CI, 0.52-0.9; P = .007) and by 59% in ATTRv-CM (HR, 0.41; 95% CI, 0.21-0.81; P = .01). All-cause mortality was likewise reduced through month 42 with HRs of 0.7 (95% CI, 0.5-0.98; P = .04) and 0.41 (95% CI, 0.19-0.93; P = .03) in the ATTRwt-CM and ATTRv-CM groups, respectively.2

In patients with ATTRv-CM receiving acoramidis, sTTR increased at day 28, reaching comparable levels to participants with ATTRwt-CM receiving acoramidis. This was despite a roughly 25% lower sTTR level in the ATTRv-CM population at baseline. However, an increase in NT-proBNP was observed over 30 months in the placebo arms; the increase was numerically greater among patients with ATTRv-CM than those with ATTRwt-CM.2

Investigators concluded that a consistent clinical benefit was displayed across multiple endpoints, including all-cause mortality, functional status, cardiovascular health, NT-proBNP, serum TTR, and quality of life in both the ATTRwt-CM and ATTRv-CM groups. The team notes the reinforcement of acoramidis’s therapeutic benefit based on these data.2

“Acoramidis may have the potential for ATTR disease primary prevention in carriers of pathogenic TTR variants,” Alexander and colleagues wrote. “This concept is currently being evaluated in the ACT-EARLY clinical trial. In addition, further studies are warranted to evaluate the efficacy of acoramidis in transthyretin-mediated polyneuropathy, based on the assumption that near-complete TTR stabilization may confer therapeutic benefits similar to those observed in ATTR-CM.”2

References

1. BridgeBio. Acoramidis significantly reduces all-cause mortality in the overall attr-cm variant and v142i (v122i) populations. November 8, 2025. Accessed November 14, 2025. https://investor.bridgebio.com/news/news-details/2025/Acoramidis-Significantly-Reduces-All-cause-Mortality-in-the-Overall-ATTR-CM-Variant-and-V142I-V122I-Populations/default.aspx

2. Alexander K, Davis M, 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. November 08, 2025. Accessed November 14, 2025. doi:10.1001/jamacardio.2025.4477