Vutrisiran: Pain in Extremity

Vutrisiran: Pain in Extremity

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 Summary

Index

Clinical Data – Global Safety Database – Label Information – Abbreviations – References

 Clinical Data

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

Pain in Extremity

Pain in extremity events during the HELIOS‑A study were reported using the following preferred terms: “Pain in Extremity” and “Limb Discomfort”. During the 18-month treatment period, pain in extremity was reported as an AE in 18 patients (14.8%) in the vutrisiran group, 3 patients (7.1%) in the patisiran group, and 8 patients (10.4%) in the APOLLO-placebo group.1 The AEs were mild or moderate in severity, and none of them led to treatment discontinuation. Pain in extremity AEs did not increase over time.2

 Global Safety Database

A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify any safety concerns involving pain in extremity with the use of vutrisiran.4

 Amvuttra Prescribing Information – Relevant Content

For relevant labeling information, please refer to the following section of the AMVUTTRA Prescribing Information5:

• ADVERSE REACTIONS Section 6.1 Clinical Trials Experience

 Abbreviations

AE = adverse event; hATTR-PN = hereditary transthyretin amyloidosis with polyneuropathy; IV = intravenous; mNIS+7 = modified Neuropathy Impairment Score +7.

Updated 2 September 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.  European Medicines Agency. Amvuttra : EPAR – Risk management plan. Published October 30, 2018. Updated June 12, 2025. Accessed September 2, 2025. https://www.ema.europa.eu/en/documents/rmp/amvuttra-epar-risk-management-plan_en.pdf.

3.  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

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

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