Vutrisiran: Post-Orthotopic Liver Transplant

Vutrisiran: Post-Orthotopic Liver Transplant

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The full Prescribing Information for AMVUTTRA® (vutrisiran) is provided here. Alnylam Pharmaceuticals does not recommend the use of its products in any manner that is inconsistent with the approved Prescribing Information. This resource may contain information that is not in the approved Prescribing Information.

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 Summary

Index

Label Information – Clinical Data – Abbreviations – References

AMVUTTRA Prescribing Information – Relevant content

The CLINICAL PHARMACOLOGY section provides the following information3:

Pharmacokinetics

Specific Populations

No clinically significant differences in the pharmacokinetics of vutrisiran were observed based on age, sex, race, mild and moderate renal impairment (eGFR≥30 to <90 mL/min/1.73 m2), or mild (total bilirubin ≤1 x ULN and AST >1 x ULN, or total bilirubin >1.0 to 1.5 x ULN and any AST) and moderate (total bilirubin >1.5 to 3 × ULN and any AST) hepatic impairment. Vutrisiran has not been studied in patients with severe renal impairment, end-stage renal disease, severe hepatic impairment, or in patients with prior liver transplant.

Clinical data

Phase 3 HELIOS-A Study

HELIOS-A was a phase 3, global, randomized, open-label study designed to evaluate the efficacy and safety of vutrisiran in patients with hATTR-PN. Patients were randomized (3:1) to receive either vutrisiran 25 mg every 3 months by subcutaneous injection (n=122) or patisiran 0.3 mg/kg every 3 weeks by IV infusion (as a reference group, n=42) for 18 months. This study used the placebo arm of the APOLLO study as an external control arm (n=77) for the primary endpoint and most other efficacy endpoints. The primary endpoint was the change from baseline in mNIS+7 at 9 months.1

Exclusion Criteria

Patients were excluded from the study if any of the following criteria applied1:

      Had a liver transplant or were likely to undergo liver transplantation during the 18-month treatment period of the study

Phase 3 HELIOS-B Study

HELIOS-B was a phase 3, global, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of vutrisiran in patients with ATTR-CM, including both hATTR and wtATTR. Patients were randomized (1:1) to receive either vutrisiran 25 mg (n=326) or placebo (n=329) every 3 months by subcutaneous injection for up to 36 months. The primary endpoint was the composite endpoint of all-cause mortality and recurrent CV events (CV hospitalizations and urgent heart failure visits) at the end of the double-blind exposure period in the overall population and in the vutrisiran monotherapy population (patients not receiving tafamidis at baseline).4

Exclusion Criteria

Patients were excluded from the study if any of the following criteria applied2:

      Prior or anticipated (during the first 12 months after randomization) heart, liver, or other organ transplant or implantation of left-ventricular assist device

 Abbreviations

AST = aspartate aminotransferase; ATTR-CM = transthyretin amyloidosis with cardiomyopathy; CV = cardiovascular; eGFR = estimated glomerular filtration rate; hATTR = hereditary transthyretin amyloidosis; hATTR-PN = hereditary transthyretin amyloidosis with polyneuropathy; IV = intravenous; mNIS+7 = modified neuropathy impairment score +7; ULN = upper limit of normal; wtATTR = wild-type transthyretin amyloidosis.

Updated 21 March 2025

References

1.  Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023;30(1):18-26. doi:10.1080/13506129.2022.2091985

2.  Protocol for: Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N Engl J Med. 2025;392(1):33-44. doi:10.1056/NEJMoa2409134

3.  AMVUTTRA (vutrisiran) Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.

4.  Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N Engl J Med. 2025;392(1):33-44. doi:10.1056/NEJMoa2409134