Acoramidis Lowers Mortality in Wild-Type and Variant Amyloid Cardiomyopathy

This article originally appeared on HCPLive^®. This version has been lightly edited.

Acoramidis reduced all-cause mortality (ACM) in individuals with amyloid cardiomyopathy (ATTR-CM) with either wild-type (ATTRwt-CM) or pathogenic variant (ATTRv-CM) forms, with effects consistent through month 42 of the ATTRibute-CM open-label extension.¹

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, according to the authors.

“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, assistant professor of cardiovascular medicine at 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

Key Outcomes Through Month 42

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, with 611 included in a modified intent-to-treat (mITT) population. Of these patients, 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 vs 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 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 noted 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,” the researchers 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. Acoramidis significantly reduces all-cause mortality in the overall attr-cm variant and v142i (v122i) populations. News release. BridgeBio. November 8, 2025. Accessed November 26, 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 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. Published online November 8, 2025. Accessed November 26, 2025. doi:10.1001/jamacardio.2025.4477