Treatment with vutrisiran was associated with fewer GI AEsa vs placebo in patients with ATTR-CM
Urey MA, et al. Presented at HFSA 20251. For the full study design and primary outcomes, see the primary HELIOS-B publication (Fontana M, et al. N Engl J Med. 2025;392:33–44).
Exploratory analysis; no confirmatory efficacy conclusions can be drawn. Adverse events were self-reported and not adjudicated, which may limit interpretation.
Compared with placebo, GI AE rates with vutrisiran were:
Patients were randomised 1:1 to vutrisiran or placebo. n (vutrisiran vs placebo): overall 326 vs 328; monotherapy 196 vs 199; baseline tafamidis 130 vs 129.
lower in the overall population
(95% CI 0.49–0.70)
nominal P<0.0001
lower in the monotherapy population
(95% CI 0.49–0.79)
nominal P<0.0001
lower in the baseline tafamidis subgroup
(95% CI 0.39–0.67)
nominal P<0.0001
CONSISTENT BY ATTR GENOTYPE
RR, 0.38 (95% CI 0.21–0.68); nominal P=0.0012
RR, 0.59 (95% CI 0.49–0.72); nominal P<0.0001
Why this matters
ATTR and amyloid deposition
ATTR is caused by misfolded TTR accumulating in multiple tissues and is associated with high mortality and morbidity
Extracardiac involvement
Patients with ATTR-CM can experience disease manifestations beyond the heart, including GI events
GI symptoms
Nausea, vomiting, diarrhea, and constipation can have a large impact on quality of life
Objective
This post hoc safety analysis assesses whether vutrisiran was associated with fewer GI events vs placebo in ATTR-CM
Reductions in GI AE rates were observed by Month 3 of the double-blind period in all populations
Mean cumulative GI events per patient in the overall population. Consistent reductions were observed in the monotherapy population and baseline tafamidis subgroup (not shown)
0.58 (0.49–0.70)
nominal P<0.0001
A Poisson regression model generated the rate ratio, 95% CI, and P-values; covariates comprised treatment group, log-transformed NT-proBNP, ATTR type, NYHA class, and age group, with the logarithm of follow-up time entered as an offset variable. Within the overall population, baseline tafamidis use and its interaction with treatment were additionally included as covariates. Lines are truncated once fewer than 5 patients remain at risk.
| Month | Placebo | Vutrisiran |
|---|---|---|
| 0 | 0.00 | 0.00 |
| 3 | 0.10 | 0.06 |
| 6 | 0.20 | 0.12 |
| 9 | 0.30 | 0.17 |
| 12 | 0.40 | 0.22 |
| 15 | 0.50 | 0.28 |
| 18 | 0.60 | 0.33 |
| 21 | 0.70 | 0.39 |
| 24 | 0.80 | 0.45 |
| 27 | 0.90 | 0.50 |
| 30 | 1.00 | 0.56 |
| 33 | 1.10 | 0.62 |
| 36 | 1.18 | 0.67 |
| 39 | 1.25 | 0.72 |
Lower rates across many different GI events
RR (vutrisiran vs placebo) in the overall population. A value below 1 favors vutrisiran
Unadjusted RR; a value <1 favors vutrisiran. Overall population (N=654). Individual-event 95% CIs were not reported.
In summary
GI AE rates were lower in patients receiving vutrisiran vs those receiving placebo during the double-blind period. Reductions in rates were observed by Month 3
Consistent results were observed across the study populations and in patients with either hATTR or wtATTR
LIMITATIONS, REFERENCES AND ABBREVIATIONS
Exploratory analysis; no confirmatory efficacy conclusions can be drawn. Adverse events were self-reported and not adjudicated, which may limit interpretation.
1. Urey MA, et al. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting, September 26–29, 2025. aGI AEs were coded using MedDRA v23.0 preferred terms. AE, adverse event; ATTR, transthyretin amyloidosis; ATTR-CM, transthyretin amyloidosis with cardiomyopathy; CI, confidence interval; GI, gastrointestinal; hATTR, hereditary transthyretin amyloidosis; HFSA, Heart Failure Society of America; MedDRA, Medical Dictionary for Regulatory Activities; NT-proBNP, N-terminal pro B-type natriuretic peptide; NYHA, New York Heart Association; RR, rate ratio; TTR, transthyretin; wtATTR, wild-type transthyretin amyloidosis.
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