Vutrisiran: Impact on Thyroid Function

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Summary

 While TTR has a role in transporting thyroxine, no clinically relevant impact on thyroid function has been observed with vutrisiran.1

o Across vutrisiran clinical studies, including the phase 3 HELIOS-A and HELIOS-B studies, thyroid-related AEs were not identified as common AEs with vutrisiran treatment.2–4

o Patients who had untreated hypothyroidism or hyperthyroidism were excluded from the phase 3 studies. Full physical examinations, including examinations of the throat and thyroid, were conducted at screening for both studies and during the treatment period for HELIOS‑A.5,6

 A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify any safety concerns with thyroid-related AEs and vutrisiran treatment.7

Index

Clinical Data – Global Safety Database – Abbreviations – References

Clinical Data

Pooled Safety Analysis of HELIOS-A and HELIOS-B

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

The HELIOS-A vutrisiran group consisted of 160 patients who received at least one dose of vutrisiran in the initial 18-month treatment period (n=122) or initially received patisiran in the treatment period and were re-randomized to receive vutrisiran during the RTE (n=38). The HELIOS-B vutrisiran group consisted of 547 patients who received at least one dose of vutrisiran during the double-blind treatment period (n=326) or initially received placebo during the double-blind period and transitioned to vutrisiran in the OLE (n=221).2

In the pooled safety analysis, thyroid-related AEs were not identified as common AEs from vutrisiran treatment. There were no safety concerns identified with thyroid-related AEs and vutrisiran treatment.2

Global Safety Database

A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify any safety concerns involving thyroid function related to vutrisiran.7

Abbreviations

AE = adverse event; ATTR = transthyretin amyloidosis; OLE = open-label extension; RTE = randomized treatment extension; TTR = transthyretin.

Updated 18 November 2025

References

1. Grogan M, Sheikh FH, Sperry BW, et al. Realizing the therapeutic potential of rapid knockdown of transthyretin via RNA interference in transthyretin amyloidosis. Mol Ther Nucleic Acids. 2025;36(3). doi:10.1016/j.omtn.2025.102590

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: Advances. 2025;4(9). doi:10.1016/j.jacadv.2025.102066

3. 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

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

5. Alnylam Pharmaceuticals. Data on file. MED-ALL-TTRSC02-2300015.

6. Alnylam Pharmaceuticals. Data on file. MED-US-TTRSC02-1900007.

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


MED-ALL-VUTRI-2500058 1.0 Approved through Nov 2027

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