Acoramidis Reduces Mortality in Amyloid Cardiomyopathy Up to 42 Months: Study

“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,” said Kevin Alexander, M.D., of Stanford University School of Medicine, U.S., and first author of the JAMA Cardiology manuscript. “The 69% reduction in all-cause mortality observed with acoramidis is clinically meaningful, with sustained and statistically significant benefits in survival, functional capacity, and quality of life. These results are encouraging for individuals with variant ATTR-CM and reflect progress in advancing precision medicine and promoting equity in cardiovascular care."

Details from the JAMA Cardiology manuscript, Efficacy of Acoramidis in Wild-Type and Variant Transthyretin Amyloid Cardiomyopathy: Results from ATTRibute-CM and its Open-Label Extension, include:

• Building upon previously presented data, which showed a 59% reduction in the risk of ACM or first cardiovascular-related hospitalization (CVH) versus placebo in the overall variant population through Month 30, this analysis observed an even greater 69% reduction in the risk of ACM or first CVH in the V142I population through Month 30

• There was also a consistent benefit to V142I patients through Month 42, with a 69% reduction in the risk of ACM for acoramidis patients compared to patients initially randomized to placebo

• The manuscript also summarizes the 59% risk reduction in ACM previously reported in variant patients through Month 42, as well as the meaningful benefits in functional capacity and quality of life measurements for variant patients, which is the first report of clinical benefit of this magnitude observed in this high-risk population with significant unmet need. This data includes:

• 6-minute walk distance with a least-squares mean difference of 87 meters (p = 0.0048) in favor of acoramidis through Month 30

• Kansas City Cardiomyopathy Questionnaire Overall Summary score, a patient-reported outcome measure that assesses the health status of individuals with heart failure, with a least-squares mean difference between of 20 points (p = 0.0019) in favor of acoramidis through Month 30

• This data was also shared in two moderated digital posters at the AHA Scientific Sessions 2025 titled, Acoramidis Effect on All-Cause Mortality in Patients with p.V142I (V122I) Variant ATTR-CM: Findings from the ATTRibute-CM Study, presented by Marianna Fontana, M.D., Ph.D. of University College London, UK and Acoramidis Reduces All-Cause Mortality and First Cardiovascular Hospitalization in Patients with Variant Transthyretin Amyloid Cardiomyopathy: Results from the ATTRibute-CM Study, presented by Prem Soman, M.D., Ph.D. of University of Pittsburgh School of Medicine, U.S.

“There was a time when I couldn’t understand why I was losing my strength – why simple things that used to come easily suddenly felt so hard. Living with ATTR-CM means facing a disease that quietly steals pieces of your life,” said Mike Lane, Founder, Amyloidosis Army, an advocacy group focused on serving the variant ATTR-CM community. “That’s why every bit of progress in this field matters so much. When I see new results and real advances, especially data like this in the variant population, I feel something I haven’t felt in a long time: hope. Hope that change is possible. Hope that science is finally catching up to the urgency of our lives.”

In addition to these moderated digital posters on the variant population, eight other digital posters were shared on the open-label extension data from ATTRibute-CM and real-world evidence. These findings included:

• Acoramidis Reduces All-Cause Mortality and Cardiovascular-Related Hospitalizations Through Month 42 in Transthyretin Amyloid Cardiomyopathy Across All Pre-specified Patient Subgroups, presented by Lily Stern, M.D. of Cedars-Sinai Heart Institute, U.S.

• The long-term benefit of acoramidis was consistently shown in patients initially randomized to acoramidis treatment compared with placebo to acoramidis switch after 30 months across multiple clinically relevant subgroups, underscoring the importance of early initiation of acoramidis to reduce the long-term risk of ACM or CVH

• Acoramidis Lowers NT-proBNP in a Larger Proportion of ATTRibute-CM Study Participants with Transthyretin Amyloid Cardiomyopathy Compared with Placebo, Independent of Atrial Fibrillation Status, presented by Mathew Maurer, M.D. of Columbia University Irving Medical Center, U.S.

• In ATTRibute-CM, the proportion of participants with improved N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Month 30 was consistently around 15 percentage points higher with acoramidis than placebo, regardless of atrial fibrillation (AF)/atrial flutter (AFL) status at baseline or during the study. The ongoing open-label extension study may offer insights into the durability of this effect and its long-term clinical consequences

• Geographic Disparities in Transthyretin Amyloid Cardiomyopathy Prevalence in United States Veterans, presented by Sandesh Dev, M.D. of Southern Arizona VA Health Care System, U.S.

• The documented prevalence of ATTR-CM increased over time in U.S. veterans, though geographic disparities exist at the state level that appear to correlate with access to amyloidosis centers. For regions with lower-than-expected prevalence, strategies are needed to address regional disparities in disease awareness, diagnosis, and access to care

• Demographic Disparities in Tafamidis Treatment and Clinical Outcomes Across the United States, presented by Nicole Cyrille-Superville, M.D. of Atrium Health Sanger Heart & Vascular Institute Kenilworth, Charlotte, NC, U.S.

• This large-scale analysis of a U.S. cohort suggests existing gender and racial disparities in tafamidis treatment initiation and outcomes in ATTR-CM. White women had the lowest rates of tafamidis initiation, while Black women had the worst clinical outcomes, highlighting a compounded disparity in treatment and survival by gender and race. These findings underscore the urgent need to address demographic-based disparities and ensure equitable care for all patients with ATTR-CM

• Serum Transthyretin Levels at Day 28 are Associated with Cardiovascular Outcomes: Insights from the ATTRibute-CM Study, presented by Nitasha Sarswat, M.D. of UChicago Medicine, U.S.

• Across treatment groups, serum TTR levels above normal range (≥20 mg/dL) at Day 28 were associated with a lower risk of cardiovascular outcomes at Month 30, when compared with serum TTR levels below normal range (<20 mg/dL). Thus, these observations demonstrate that higher serum TTR levels over time may have the potential for clinical benefits in both CVM and CVH

• Acoramidis Improved Clinical Outcomes, Function, Quality of Life and NT-proBNP in Patients with Transthyretin Amyloid Cardiomyopathy Regardless of Atrial Fibrillation Status at Baseline, presented by Richard Cheng, M.D. of University of Washington, Seattle, WA, U.S.

• Acoramidis improved clinical outcomes (ACM, CVH), functional status, quality of life, and NT-proBNP levels relative to placebo in participants with ATTR-CM, regardless of AF/AFL diagnosis at baseline

• Acoramidis Reduces the Risk of All-Cause Mortality and Cardiovascular-Related Hospitalization Compared with Placebo in Participants with Transthyretin Amyloid Cardiomyopathy and Early-Stage Heart Failure Regardless of Atrial Fibrillation History: Insights from ATTRibute-CM, presented by Ronald Witteles, M.D. of Stanford University School of Medicine, U.S.

• Lower risk of clinical outcomes (ACM and CVH) was observed with acoramidis in patients with early-stage heart failure, regardless of the presence or absence of an AF/AFL diagnosis at baseline

• Vutrisiran Healthcare Resource Utilization, Costs, Discontinuation, and Mortality: A Retrospective Database Analysis, presented by Nicole Bart, M.D., Ph.D. of St. Vincent's Hospital Sydney, AU

• One-third to half of pts presented to the hospital within 1.5 y of vutrisiran treatment (before ATTR-CM approval); within 12 months, roughly 1 in 4 died or discontinued therapy for ≥90 d past the 90-day administration schedule, with many switching to other ATTR treatments. This suggests that vutrisiran-treated patients continue to experience significant HCRU and costs related to disease progression despite treatment. A need remains for new therapies to further reduce burden and costs

Acoramidis is approved as Attruby® by the U.S. FDA and is approved as BEYONTTRA® by the European Medicines Agency (EMA) , Japanese Pharmaceuticals and Medical Devices Agency, and the UK Medicines and Healthcare Products Regulatory Agency with all labels specifying near-complete stabilization of TTR.

More data on the benefit of Attruby for ATTR-CM patients is planned for future medical meetings.

Reference:

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 08, 2025. doi:10.1001/jamacardio.2025.4477