Givosiran: Use in Patients with Pre-Existing Hepatic Impairment

Givosiran: Use in Patients with Pre-Existing Hepatic Impairment

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The full Prescribing Information for GIVLAARI® (givosiran) 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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 Index

Clinical Data – Label Information – Abbreviations – References

 Clinical data

The ENVISION study was a phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of givosiran in patients with a documented diagnosis of AHP. Enrolled patients were randomized on a 1:1 basis to receive subcutaneous injections of givosiran 2.5 mg/kg (N=48) or placebo (N=46) once a month for 6 months, followed by an optional 30-month OLE. The primary endpoint was the annualized rate of composite porphyria attacks among patients with AIP at 6 months.1

Key study exclusion criteria were:2

• ALT >2×ULN
• Total bilirubin >1.5×ULN. Patients with elevated total bilirubin that was secondary to documented Gilbert’s syndrome were eligible if the total bilirubin was <2×ULN.
• On an active liver transplant waiting list, or anticipated to undergo liver transplantation during the blinded study treatment period

 Givlaari Prescribing Information – Relevant content

The CLINICAL PHARMACOLOGY section provides the following information3:

Specific Populations

No clinically meaningful differences in givosiran pharmacokinetics or pharmacodynamics (percent reduction in urinary ALA and PBG) were observed based on age (19 to 65 years), sex, race/ethnicity, mild, moderate or severe renal impairment (eGFR ≥15 to ˂89 mL/min/1.73m2 estimated by the Modification of Diet in Renal Disease [MDRD] formula), and mild hepatic impairment (bilirubin ≤1×ULN and AST >1×ULN, or bilirubin >1×ULN to 1.5×ULN).The effect of end-stage renal disease (eGFR <15 mL/min/1.73m2), and moderate to severe hepatic impairment on givosiran pharmacokinetics is unknown.

 Abbreviations

AHP = acute hepatic porphyria; AIP = acute intermittent porphyria; ALA = aminolevulinic acid; ALT = alanine aminotransferase; eGFR = estimated glomerular filtration rate; MDRD = Modification of Diet in Renal Disease; PBG = porphobilinogen; ULN = upper limit of normal; OLE = open-label extension.

Updated 02 January 2025

 References

1.  Kuter DJ, Bonkovsky HL, Monroy S, et al. Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial. J Hepatol. 2023;79(5):1150-1158. doi:10.1016/j.jhep.2023.06.013

2.  Supplement to: Balwani M, Sardh E, Ventura P, et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N Engl J Med. 2020;382(24):2289-2301. doi:10.1056/NEJMoa1807838

3.  GIVLAARI (givosiran) Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.