ATTRibute-CM: Acoramidis Reduces Cardiovascular Mortality and Hospitalization with Ahmad Masri, MD

Acoramidis significantly reduced cumulative cardiovascular mortality (CVM) and recurrent cardiovascular-related hospitalization (CVH) over 30 months in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), based on an exploratory analysis of ATTRibute-CM.1

Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025 by Ahmad Masri, MD, director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, this analysis also revealed surprisingly rapid changes in both endpoints, reaching significance after the first month.1

The editorial team at HCPLive sat down with Masri to discuss the exploratory analysis, its findings, and the implications for treating the underserved ATTR-CM patient population.

“One important point that emerged – and these are all exploratory analyses – is the timing when you start to see those events accruing in the acoramidis arm versus placebo,” Masri told HCPLive. “We usually think of this disease as needing some time to confer some benefit to patients on the drug. However, what we’ve seen here is that once you start acoramidis, within a few months, even as early as the first month, you start to accrue fewer events than placebo.”

ATTRibute-CM, a phase 3, double-blind clinical trial, saw investigators randomly assign patients with ATTR-CM in a 2:1 ratio to either acoramidis 800 mg twice daily or matching placebo. The trial lasted 30 months, with a 4-step primary hierarchical analysis endpoint consisting of all-cause mortality, CVH, change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and change from baseline in 6-minute walk distance.2

Patients were eligible if they had an established diagnosis of ATTR-CM and clinical heart failure with ≥1 previous hospitalization for heart failure, volume overload, or heart failure resulting in diuretic treatment. Patients also had to have a 6-minute walk distance of ≥150 m on ≥2 tests performed between 24 hours and 3 weeks apart, a level of NT-proBNP of ≥300 pg/mL, and a left ventricular wall thickness of ≥12 mm on a previous imaging study.2

Ultimately, 632 patients underwent randomization, with 421 assigned to acoramidis and 211 to placebo. Mean age was 77 +/- 6.6 years, 90.2% of participants were men, and 90.3% of patients had wild-type TTR. Most patients also had either New York Heart Association class II (72%) or III (17.2%) symptoms.2

Investigators found that acoramidis outperformed placebo by a win rate of 1.8 (95% CI, 1.4-2.2) based on the 4-step hierarchical analysis. CVM and CVH contributed over half of the wins and losses to the win ratio, while NT-proBNP pairwise comparisons showed the highest ratio of wins to losses.2

Masri and colleagues’ exploratory analysis found that CVM and CV-related hospitalization occurred in 33.3% (136) of participants in the acoramidis arm versus 98 (48.5%) in the placebo group. Acoramidis also substantially reduced the risk of cumulative CVM or recurrent CVH compared to placebo (hazard ratio [HR], 0.51; 95% CI, 0.43-0.62; P <.0001). Masri and colleagues observed treatment effects beginning at Day 16, which continued to improve through month 30. Difference in mean cumulative events reached 53 per 100 participants (95% CI, 29-79; P <.001) at month 30.1

“I think this is the most important takeaway of what we have presented,” Masri said of the early cumulative event change. “Usually, there is no urgency on average for getting a diagnosis of transthyretin amyloidosis. People in general think of it as more of a chronic disease, and that 6 months’ delay is not going to make a huge difference for initiating therapy. I think this analysis actually challenges that.”

References

1. Masri A, Judge D, Ruberg F, et al. Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis from ATTRibute-CM. Presented at the Heart Failure Society of America Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.

2. Razvi Y, Judge DP, Martinez-Naharro A, et al. Effect of Acoramidis on Myocardial Structure and Function in Transthyretin Amyloid Cardiomyopathy: Insights From the ATTRibute-CM Cardiac Magnetic Resonance (CMR) Substudy. Circ Heart Fail. 2024;17(12):e012135. doi:10.1161/CIRCHEARTFAILURE.124.012135