Vutrisiran: Dyspnea
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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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In the HELIOS-A study, dyspnea was reported in 8 patients (6.6%) treated with vutrisiran and 0 patients in the APOLLO placebo group over the 18‑month treatment period; the events were mild or moderate in severity.1 In the HELIOS-B study, dyspnea was reported in 43 patients (13%) treated with vutrisiran and 51 patients (16%) in the placebo group during the double-blind treatment period.2 A cumulative post-marketing review of Alnylam’s global safety database did not identify any safety concerns involving dyspnea with the use of vutrisiran.3 No additional information is available regarding dyspnea events and their management. |
Clinical Data – Global Safety Database – Abbreviations – References
HELIOS-A
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.4
Safety Results: Dyspnea
Dyspnea events during the HELIOS-A study were reported using the following preferred terms: Dyspnea, Dyspnea exertional, and Dyspnea paroxysmal nocturnal. At 18 months of the HELIOS-A study, dyspnea AEs were reported in 8 patients (6.6%) treated with vutrisiran and 0 patients in the APOLLO placebo group. The AEs were mild to moderate in severity and did not lead to treatment interruption, treatment discontinuation, or withdrawal from a clinical study. The frequency of dyspnea AEs did not increase over time.1 None of the dyspnea AEs were determined by the investigator to be related to treatment.5
HELIOS-B
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 treatment period in the overall population and in the monotherapy population (patients not receiving tafamidis at baseline). After the double-blind treatment period, all eligible patients remaining on the study were allowed to receive vutrisiran in an OLE.6
Safety Results: Dyspnea
During the double-blind treatment period of the HELIOS-B study, dyspnea AEs were reported in 43 patients (13%) treated with vutrisiran and 51 patients (16%) in the placebo group.2
A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify any safety concerns involving dyspnea with the use of vutrisiran.3
AE = adverse event; ATTR-CM = transthyretin amyloidosis with cardiomyopathy; CV = cardiovascular; hATTR = hereditary transthyretin amyloidosis; hATTR-PN = hereditary transthyretin amyloidosis with polyneuropathy; IV = intravenous; mNIS+7 = modified Neuropathy Impairment Score +7; OLE = open-label extension; wtATTR = wild-type transthyretin amyloidosis.
Updated 07 October 2025
1. Alnylam Pharmaceuticals. Data on file. MED-ALL-TTRSC02-2500016.
3. Alnylam Pharmaceuticals. Data on file. MED-ALL-VUTRI-2500021.
5. Alnylam Pharmaceuticals. Data on file. MED-ALL-TTRSC02-2200045.
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MED-US-TTRSC02-2200061 8.0 Approved through Mar 2027 |
