Givosiran: Use in Pediatric Patients
Givosiran: Use in Pediatric Patients
Givosiran: Use in Pediatric Patients
The following information is provided in response to your unsolicited inquiry. It is intended to provide you with a review of the available scientific literature and to assist you in forming your own conclusions in order to make healthcare decisions. This document is not for further dissemination or publication without authorization.
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.
If you are seeking additional scientific information related to Alnylam medicines, you may visit the Alnylam US Medical Affairs website at RNAiScience.com.
Summary
o Per the ENVISION study protocol, patients ≥12 years of age were eligible to be included in the study and the youngest patient enrolled was 19 years of age.1,2 The ELEVATE registry (NCT04883905) is a global, prospective, observational study designed to characterize the real-world long-term safety and efficacy of givosiran and to describe the natural history and management of patients with AHP.3,4 o The youngest patient enrolled that received givosiran was 14 years of age.4 Prospective data collection is ongoing.3,4 Case reports on the use of givosiran in pediatric patients are provided below. |
Clinical Data – Case Reports – Label Information – Abbreviations – References
ENVISION Study
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
Per the ENVISION study protocol, patients ≥12 years of age were eligible to be included in the study.2 The youngest patient enrolled in the study was 19 years of age, as shown in Table 1.1
Table 1. Age of Enrolled Patients at Baseline in ENVISION.1
Placebo crossover (n=46) | Continuous givosiran (n=48) | All givosiran (N=94) | |
Age at screening, years, median (range) | 36.0 (20-60) | 42.0 (19-65) | 37.5 (19-65) |
ELEVATE Registry
The ELEVATE registry (NCT04883905) is a global, prospective, observational study designed to characterize the real-world long-term safety and efficacy of givosiran and to describe the natural history and management of patients with AHP. Patient demographic characteristics at enrollment are available for 166 patients, the youngest patient enrolled that received givosiran was 14 years of age.3,4
Prospective data collection is ongoing.3,4 No additional data from clinical studies are available regarding the use of givosiran in pediatric patients.
The following information provides an overview of published case reports of pediatric patients who received givosiran. It is not intended to be an all-inclusive list or summary of relevant publications, abstracts, and manuscripts.
Phyo ZH, Keates-Baleeiro JA. Diagnosis and management of acute intermittent porphyria in teenage fraternal twins. Medical reports. 2026;19. doi:10.1016/j.hmedic.2026.1004775
A case series discussed dizygotic 15-year-old female twins who presented at different times with acute abdominal and hip pain, hypertension, and tachycardia with symptoms temporally associated with menses and reduced oral intake. Based on clinical presentation and family history of AIP, random urine ALA and PBG levels were obtained, which were elevated. The patients were diagnosed with AIP with heterozygous deletion in HMBS.
Both patients were initially treated with hemin 4 mg/kg/day for 4 days for their acute attacks and transitioned to monthly hemin prophylaxis, followed by initiation of givosiran 2.5 mg/kg monthly.
Rudnick SB, West NE, Fong K, Beaven SW, VanderVeen NT. Acute intermittent porphyria in an adolescent patient: Diagnostic and treatment challenges. Cureus. 2024;16(11):e74784. Published 2024 Nov 29. doi:10.7759/cureus.747846
A case report discussed a 17-year-old previously heathy female patient with multiple presentations to the hospital for intense bouts of abdominal pain, nausea, vomiting, and seizure-like activity. On a later admission, porphyria tests were performed and a diagnosis of AIP was made. Genetic analysis confirmed a heterozygous mutation in the HMBS gene.
The patient was started on IV hemin 3 mg/kg/day for 4 days, then increased to 4 mg/kg/day for 14 days due to suboptimal treatment response.
The patient was also started on givosiran 2.5 mg/kg SC once monthly, and discharged home after her pain was adequately controlled and the porphyria flare was treated.
Bujold KE, Kasher N, McKiernan C. Givosiran for the treatment of pediatric acute intermittent porphyria. J Pediatr Hematol Oncol.2024;46(7):e524‑e527. doi:10.1097/MPH.00000000000029417
A case report discussed the use of givosiran in a 16-year-old female patient with medical history of anorexia nervosa who was admitted to the hospital for worsening generalized abdominal pain with bilateral radiation to the back, intermittent non-bloody nonbilious emesis, pleuritic chest pain, and constipation. Three months later, the patient was admitted to the hospital with a similar presentation. Urine PBG, total plasma porphyrins, and urine PBG:creatinine ratio were elevated, consistent with AHP.
She received IV carbohydrate loading and hemin infusions. The pathogenic variant c.77G>A (p.Arg26His) of the HMBS gene was later identified with confirmatory genetic testing.
Over the next 3 months, the patient was treated with 2 additional hemin infusions for AIP attacks and later started on givosiran due to the frequency and severity of her attacks.
Mazzoli M, et al. Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: A case report. Eur Rev Med Pharmacol Sci. 2024;28(8):3268-3274. doi:10.26355/eurrev_202404_360558
A case report detailed the treatment outcome of a 12-year-old patient with AIP and severe chronic porphyric neuropathy. The patient was diagnosed at 5 years of age after an acute porphyric attack; genetic analysis confirmed a pathogenic mutation in the HMBS gene.
The patient was initially treated with routine heme arginate infusions and continued to experience frequent porphyric attacks. Givosiran treatment was initiated at 2.5 mg/kg monthly.
Givlaari Prescribing Information – Relevant Content
The INDICATIONS AND USAGE section provides the following information9:
GIVLAARI is indicated for the treatment of adults with acute hepatic porphyria (AHP).
The USE IN SPECIFIC POPULATIONS section provides the following information9:
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
ADP = ALAD deficient porphyria; AHP = acute hepatic porphyria; AIP = acute intermittent porphyria; ALA = aminolevulinic acid; CT = computed tomography; HCP = hereditary coproporphyria; HMBS = hydroxymethylbilane synthase; IV = intravenous; OLE = open-label extension; PBG = porphobilinogen; QOL = quality of life; SAE = serious adverse event; VP = variegate porphyria.
Updated 24 August 2026
9. GIVLAARI (givosiran) Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.
|
|
|
MED-ALL-AS1-2400019 6.0 Approved through Aug 2028 |
