Vutrisiran: Hypersensitivity Reactions

The following information is provided in response to your unsolicited inquiry. It is intended to provide you with a review of the available scientific literature and to assist you in forming your own conclusions in order to make healthcare decisions. This document is not for further dissemination or publication without authorization.

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.

If you are seeking additional scientific information related to Alnylam medicines, you may visit the Alnylam US Medical Affairs website at RNAiScience.com.

Summary

In the phase 3 HELIOS‑A and HELIOS-B studies, no increased risk of serious or severe hypersensitivity reaction was observed, and no specific risk factors were identified. However, as with all drugs, hypersensitivity reactions are possible. Patients should be treated appropriately for signs of hypersensitivity reactions at the clinical discretion of the healthcare provider.1
A pooled safety analysis including data from 707 patients who received at least one dose of vutrisiran at any time during the HELIOS-A and HELIOS-B studies was conducted to evaluate the safety of vutrisiran in patients with ATTR who received treatment for up to 58 months.2

Hypersensitivity was not identified as a common adverse event with vutrisiran. Adverse events were consistent with those reported for patients who received vutrisiran during the randomized periods of HELIOS-A and HELIOS-B.2

A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify safety concerns involving hypersensitivity reactions related to vutrisiran. Hypersensitivity reactions continue to be closely monitored through routine pharmacovigilance activities.3

Index

Vutrisiran Formulation and Administration – Global Safety Database – Abbreviations – References

Vutrisiran Formulation and administration Information

Patients who receive vutrisiran do not require premedication to decrease the risk of hypersensitivity reactions.4 Vutrisiran utilizes GalNAc conjugate technology as the method of drug delivery which allows for subcutaneous injection. GalNAc conjugation facilitates siRNA delivery into the liver via the ASGPR expressed on hepatocytes.5 Vutrisiran uses second generation ESC, which includes a combination of additional phosphorothioate linkages, as well as 2′‑O-methyl nucleotide and 2′‑fluoro nucleotide modifications, that provide improved molecular stability and minimized metabolic lability.6,7

Global Safety Database

A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify safety concerns involving hypersensitivity reactions related to vutrisiran. Hypersensitivity reactions continue to be closely monitored through routine pharmacovigilance activities.3

Abbreviations

ASGPR = asialoglycoprotein receptor; ATTR = transthyretin amyloidosis; ESC = enhanced stabilization chemistry; GalNAc = N‑acetylgalactosamine; siRNA = small-interfering ribonucleic acid.

Updated 6 October 2025

References

1. Amvuttra : EPAR – Risk management plan. European Medicines Agency. Published October 12, 2022. Accessed January 29, 2025. https://www.ema.europa.eu/en/documents/rmp/amvuttra-epar-risk-management-plan_en.pdf.

2. Witteles RM, Garcia-Pavia P, Morbach C, et al. Vutrisiran in transthyretin amyloidosis: a pooled safety analysis of HELIOS-A and HELIOS-B. JACC Adv. 2025;4(9). doi:10.1016/j.jacadv.2025.102066

3. Alnylam Pharmaceuticals. Data on file. MED-ALL-VUTRI-2500021.

4. 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

5. Nair JK, Attarwala H, Sehgal A, et al. Impact of enhanced metabolic stability on pharmacokinetics and pharmacodynamics of GalNAc-siRNA conjugates. Nucleic Acids Res. 2017;45(19):10969-10977. doi:10.1093/nar/gkx818

6. Janas MM, Zlatev I, Liu J, et al. Safety evaluation of 2’-deoxy-2’-fluoro nucleotides in GalNAc-siRNA conjugates. Nucleic Acids Res. 2019;47(7):3306-3320. doi:10.1093/nar/gkz140

7. Habtemariam BA, Karsten V, Attarwala H, et al. Single‐dose pharmacokinetics and pharmacodynamics of transthyretin targeting N‐acetylgalactosamine–small interfering ribonucleic acid conjugate, vutrisiran, in healthy subjects. Clin Pharmacol Ther. 2021;109(2):372-382. doi:10.1002/cpt.1974


MED-ALL-TTRSC02-2400015 3.0 Approved through Oct 2027

Download PDF