Acoramidis reduced incidence of atrial fibrillation events in patients with ATTR-CM- BridgeBio Pharma

BridgeBio Pharma Inc  presented data from ATTRibute-CM, highlighting the reduced incidence of atrial fibrillation (AF) events in the overall ATTR-CM population. These data were presented in a moderated ePoster at the Annual Congress of the Heart Failure Association of the ESC (Heart Failure 2025), taking place in Belgrade, Serbia from May 17 - 20.  Acoramidis is a selective small molecule, orally administered, near-complete (≥90%) transthyretin (TTR) stabilizer.

Details from the post-hoc analysis on incidence of AF in ATTRibute-CM included:

• Acoramidis Treatment Is Associated with a Lower Incidence of Atrial Fibrillation-related Events in Patients with ATTR-CM: A Post-hoc Analysis of the ATTRibute-CM Trial, presented by Dr. Alexander
  • AF is a common complication of ATTR-CM, observed in up to 70% of patients, and the onset of AF is associated with an increased risk of cardiovascular-related hospitalizations (CVH)
  • In ATTRibute-CM, a 43% relative risk reduction in the annual frequency of CVH due to AF/atrial flutter (AFL) was observed with acoramidis relative to placebo. In the subgroup who had no prior history of AF, a 17% lower incidence of new-onset AF/AFL was reported with acoramidis compared to placebo
  • These findings show the potential of acoramidis to reduce both disease progression, as indicated by a lower incidence of new-onset AF/AFL, and CVH morbidity caused by AF/AFL, in patients with ATTR-
  • CM

In addition to the moderated ePoster, three analyses were shared on the strong clinical outcomes in ATTRv-CM versus placebo. ATTRv-CM is associated with early age of disease onset with more advanced heart failure symptoms, which often leads to a poorer prognosis than those with wild-type ATTR-CM (ATTRwt-CM). These findings included:

• i) Acoramidis Improves Serum TTR Levels in Patients with Wild-type or Variant Transthyretin Amyloid Cardiomyopathy: Results from ATTRibute-CM, presented by  Dr. Anique Ducharme, of Université de Montréal, CAN
  • In both subgroups of ATTRv-CM and ATTRwt-CM, acoramidis treatment induced a rapid increase in serum TTR levels, a measure of TTR stability, by Day 28, with comparable serum TTR levels achieved in both subgroups from Day 28 through Month 30. Relative increases in serum TTR concentrations resulting from greater TTR stability have been associated with reduced risk of all-cause and cardiovascular mortality in the general population in recent literature  (see  citation).  
•  
  • ii) Effect of Acoramidis on Functional Capacity and Quality of Life in Patients with Variant ATTR-CM: Results from ATTRibute-CM, presented by Dr.  Marianna Fontana of University College London,
    • Data from ATTRibute-CM showed that when acoramidis was administered for 30 months, participants with ATTRv-CM had a clinically significant slower decline in functional capacity and quality of life compared with placebo, consistent with the overall results in both ATTRv-CM and ATTRwt-CM. At Month 30, the mean difference between acoramidis and placebo treatment groups in the change from baseline in 6-minute walk distance was 86.7 m (p = 0.0048) in favor of acoramidis and in the change from baseline in KCCQ-OS at Month 30, was 20.3 points (p = 0.0019) in favor of acoramidis, in patients with ATTRv-CM
    •  
• iii) Effect of Acoramidis on All-cause Mortality, Cardiovascular Hospitalization and NT-proBNP in Variant ATTR-CM: Results from ATTRibute-CM, presented by Dr. Marianna Fontana, of University College London
  • In ATTRibute-CM, acoramidis treatment administered for 30 months led to a substantial reduction (>50%) in the composite of all-cause mortality (ACM)/CVH, ACM and CVH in participants with ATTRv-CM compared to placebo. This improvement was accompanied by favorable effects on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels

Additional acoramidis moderated ePosters at Heart Failure 2025 included:

iv) Disease Progression Among Patients Receiving Tafamidis for ATTR-CM in a Real-world Setting, presented by Dr.  Daniel P. Judge  of Medical University of South Carolina, US                                                                                                                                                                                          This analysis suggests disease progression despite treatment with tafamidis in ATTR-CM. CVH was frequent, with approximately 1 in 5 tafamidis-treated patients hospitalized in the first six months of therapy. As more therapeutic options become available, measuring the clinical effectiveness of therapies in a real-world setting will be important to help inform physicians and patients when making treatment decisions

•  
• v) Cause of Death in Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): Findings from the ATTRibute-CM Study, presented by Dr.  Laura Obici,. of University of Pavia, ESP
  • In the ATTRibute-CM study, total deaths were numerically lower with acoramidis compared with placebo. The relative risk reduction of 30% in cardiovascular-related mortality by Month 30 was driven predominantly by a reduction in heart failure-related deaths
  •  
  • vi) Time from First Recorded Clinical Manifestation to Diagnosis of Transthyretin Amyloid Cardiomyopathy: A Retrospective Cohort Study Using U.S. Claims Data, presented by Dr. Joshua Mitchell, Washington University School of Medicine in St. Louis, USA
    • The median time from the first documented clinical manifestation to ATTR-CM diagnosis was almost 5 years, and over 2 years from the first heart failure diagnosis. This demonstrates that the patient journey to an ATTR-CM diagnosis can be prolonged and challenging, which potentially leads to more severe disease at diagnosis. Understanding the factors contributing to diagnostic delays is important to improving diagnostic pathways and patient outcomes
•  
• “Based on the findings from ATTRibute-CM, we believe that acoramidis has the potential to enable patients with both variant and wild-type ATTR-CM to live longer, healthier lives, especially for those with variant ATTR-CM who typically have a poorer prognosis. We observed both a striking reduction in the frequency of cardiovascular hospitalizations (which included clinic or emergency department visits for urgent heart failure management) and a clinically important and statistically significant reduction in all-cause mortality in the important subgroup. These clinical outcomes were further mirrored in robust improvements in functional capacity, quality of life and biomarkers of heart failure severity,” said Dr. Jonathan Fox,  President and Chief Medical Officer of BridgeBio Cardiorenal. “Given these compelling results, acoramidis should be considered as first-line treatment for newly diagnosed patients, and those currently on other therapies could be switched to acoramidis to maximize their potential to achieve such benefits.”
•  
• "The reduction in new-onset atrial fibrillation and AF-related hospitalizations represents an important finding for the ATTR-CM community. I am encouraged by the growing body of data from the ATTRibute-CM study, which adds to the understanding of acoramidis and its potential impact on clinical outcomes for patients. Furthermore, the observed reductions in hospitalizations and mortality, along with improvements in functional capacity and quality of life, suggest that acoramidis may offer benefit to both variant and wild-type ATTR-CM patients who have limited treatment options,” said Dr. Kevin Alexander of Stanford University School of Medicine, USA. “These data support further consideration of acoramidis as a promising front-line therapy for ATTR-CM, particularly for patients with the hereditary form of the disease, who often face rapid and severe progression.”

Citation- Christoffersen M et al. Transthyretin Tetramer Destabilization and Increased Mortality in the General Population. JAMA Cardiol. 2025, 10:155 doi: 10.1001/jamacardio.2024.4102.