Dados do Trabalho

Título

EFFICACY AND SAFETY OF LUMASIRAN FOR INFANTS AND YOUNG CHILDREN WITH PRIMARY HYPEROXALURIA TYPE 1: 30-MONTH ANALYSIS OF THE PHASE 3 ILLUMINATE-B TRIAL

Introdução

Background: Primary hyperoxaluria type 1 (PH1) is a genetic disorder resulting in excess hepatic oxalate production, which can lead to urolithiasis, systemic oxalosis, nephrocalcinosis (NC), and ultimately, chronic kidney disease/kidney failure. Lumasiran, a liver-directed RNA interference therapeutic that reduces urinary oxalate (UOx) levels, demonstrated sustained efficacy with an acceptable safety profile over 12 months in infants and young children age <6 years with PH1 participating in ILLUMINATE-B (NCT03905694).
Objective: To evaluate outcomes of lumasiran treatment through Month 30 of ILLUMINATE-B.

Material e Método

ILLUMINATE-B is an ongoing, Phase 3, multinational, open-label, single-arm study. Eligible patients had a confirmed PH1 diagnosis, were <6 years old at study entry, had an eGFR >45 mL/min/1.73m2 if ≥12 months old or normal serum creatinine if <12 months old, and UOx:creatinine (Cr) ratio greater than upper limit of normal. A primary analysis was conducted at 6 months; patients are now in an extension period (EP) of up to 54 months. Changes in NC and kidney stone event rates were exploratory endpoints.

Resultados

All 18 patients enrolled in ILLUMINATE-B entered the EP and remain in the study. At Month 30, the mean percent reduction from baseline in spot UOx:Cr ratio with lumasiran treatment was 76%. Mean percent reduction in plasma oxalate was 42% from baseline to Month 30. eGFR remained relatively stable through Month 30. In 14 patients with NC at baseline, NC grade improved in 86% (12/14) at Month 24; no patient worsened. Of the 4 patients with no baseline NC, all remained stable at Month 24. Kidney stone event rates remained low through Month 30. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients [17%]).

Discussão e Conclusões

Conclusion: In infants and young children with PH1, lumasiran treatment resulted in sustained reductions in urinary and plasma oxalate through Month 30, with an acceptable safety profile. Previous observations of stable kidney function and low kidney stone event rates were maintained through Month 30, while improvements in NC grade were maintained through Month 24.

Palavras Chave

hyperoxaluria, kidney

Área

Nefropediatria