Vutrisiran Reduces GI Event Rates in Patients with ATTR-CM

Vutrisiran substantially reduces rates of gastrointestinal (GI) events in patients with transthyretin cardiac amyloidosis with cardiomyopathy (ATTR-CM) compared to placebo, according to an analysis of the phase 3 HELIOS-B study.1

Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025 by Marcus Urey, MD, division of cardiovascular medicine, University of California San Diego Health, and colleagues, this analysis divided patients both by treatment received and by type of ATTR-CM.1

HELIOS-B was a phase 3 study investigating patients aged 18-85 years with a diagnosis of ATTR-CM and a clinical history of heart failure (HF). Participants were randomly assigned in a 1:1 ratio to receive either vutrisiran 25mg or placebo subcutaneously every 3 months for ≤36 months. Patients were also either receiving or not receiving tafamidis at baseline, with no prespecified plan to begin taking the drug during the 12 months post-randomization.2

A 24-month open-label extension was also conducted, including patients who completed the DB period of 33-36 months. These participants were given vutrisiran 25mg every 3 months for up to the full duration of the extension.2

In this analysis, Urey and colleagues found an overall reduction of 37-49% in rates of overall GI events among patients treated with vutrisiran. The monotherapy population receiving placebo experienced a total of 38.7 GI events per 100 patient-years (PY), compared to the vutrisiran monotherapy group’s 24.3 events per 100 PY. The baseline tafamidis subgroup receiving placebo saw a total of 43.1 GI events per 100 PY, while the vutrisiran and tafamidis subgroup exhibited 22.1 events per 100 PY.1

Rate ratios (RRs) for GI events increased over time, with a significantly sharper increase among placebo recipients in the overall population and across both subgroups. The overall population saw an RR of 0.58 (95% CI, 0.49-0.70; P <.0001), with the placebo group reaching a mean of 1.25 cumulative GI events per patient versus the vutrisiran group’s 0.75 events per patient by 36 months. The tafamidis subgroup receiving placebo again saw a sharper increase than other placebo groups.1

Additionally, specific GIs commonly associated with negative quality of life impacts were measured individually. Diarrhea saw a roughly 73% difference between the overall placebo and overall vutrisiran groups (4.1 vs 1.9 ER per 100PY), while nausea reached a 95% difference (3.4 vs 1.2 ER per 100PY).1

Investigators also compared patients by ATTR-CM type. The 76 patients in HELIOS-B with hereditary ATTR-CM (hATTR-CM) had an RR of 0.38 (95% CI, 0.21-0.68; P = .0012). The 578 patients with wild-type ATTR-CM (wATTR-CM) exhibited an RR of 0.59 (95% CI, 0.49-0.72; P <.0001).1

Ultimately, investigators determined that vutrisiran resulted in a substantial reduction in GI events which was statistically significant and observed early in the trial for all populations assessed.1

“These results suggest that vutrisiran may provide a treatment benefit on GI manifestations potentially caused by ATTR,” Urey and colleagues wrote. “Future trials should consider assessment of extracardiac variables to better understand the impact of treatment options outside of traditional cardiac parameters.”1

References

1. Urey M, Bui Q, Obici L, et al. Evidence of Fewer Gastrointestinal Events in ATTR-CM Patients Treated with Vutrisiran Compared with Placebo: Analysis from HELIOS-B. Presented at the Heart Failure Society of America Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.

2. Witteles RM, Garcia-Pavia P, Damy T, et al. Vutrisiran Improves Survival and Reduces Cardiovascular Events in ATTR Amyloid Cardiomyopathy: HELIOS-B. J Am Coll Cardiol. Published online April 30, 2025. doi:10.1016/j.jacc.2025.04.008