Vutrisiran: Concomitant Use with Diflunisal

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Summary

 Clinical trials that evaluate the efficacy and safety of vutrisiran with concomitant diflunisal have not been conducted to date.

o In the HELIOS-A study, patients who were previously on diflunisal must have completed a 3‑day wash-out prior to dosing.1

o In the HELIOS-B study patients who were previously on diflunisal must have completed a 30‑day wash-out prior to dosing.2

Index

HELIOS-A – HELIOS-B – 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.1

Select Exclusion Criteria

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

 Currently taking diflunisal; if previously on diflunisal, the patient must have completed a 3‑day wash‑out prior to dosing

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 period in the overall population and in the vutrisiran monotherapy population (patients not receiving tafamidis at baseline).3

Select Exclusion Criteria

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

 Currently taking diflunisal; if previously on diflunisal, the patient must have completed a 30‑day wash‑out prior to dosing

 Unwilling to avoid concurrent treatment with diflunisal

Abbreviations

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; wtATTR = wild-type transthyretin amyloidosis.

Updated 20 March 2026