Dados do Trabalho

Título

EFFICACY AND SAFETY OF LUMASIRAN IN PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1: 36-MONTH ANALYSIS OF THE ILLUMINATE-A TRIAL

Introdução

Introduction and Objective: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by hepatic oxalate overproduction leading to kidney stones and progressive kidney disease. Lumasiran is an RNAi therapeutic approved for the treatment of PH1 to lower urinary oxalate (UOx) and plasma oxalate levels in pediatric and adult patients. Here, we report data from the 36-month (M) analysis of ILLUMINATE-A, a Phase 3 trial of lumasiran (NCT03681184).

Material e Método

ILLUMINATE-A is an ongoing Phase 3 trial in patients age ≥6 years with genetically confirmed PH1 and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2. A 6M double-blind, placebo-controlled primary analysis period is followed by an extension period (up to 54M) in which all patients receive lumasiran.

Resultados

Results: Of 39 patients enrolled, 24/26 in the lumasiran/lumasiran group and 13/13 in the placebo/lumasiran group entered and continue in the extension period. Mean 24-hour UOx reduction at M36 relative to baseline was 63% in the lumasiran/lumasiran group and 55% in the placebo/lumasiran group (M30 post–lumasiran initiation). At M36, the proportion of patients achieving 24-hour UOx excretion ≤1.5 × upper limit of normal was 76% in the lumasiran/lumasiran group and 92% in the placebo/lumasiran group. Mean baseline-to-M36 reductions in plasma oxalate were 36% and 37% in the lumasiran/lumasiran and placebo/lumasiran groups, respectively. In both groups, eGFR remained stable through M36. Kidney stone event rates decreased from 3.19/person-year during the 12M before consent to 0.70/person-year in the lumasiran/lumasiran group and from 0.54/person-year to 0.39/person-year in the placebo/lumasiran group. Medullary nephrocalcinosis generally remained stable or improved. The most common lumasiran-related adverse events were mild injection-site reactions (36% of patients).

Discussão e Conclusões

Conclusions: Long-term treatment with lumasiran led to sustained UOx reduction through M36, with an acceptable safety profile in patients with PH1 and encouraging clinical outcomes data.

Palavras Chave

hyperoxaluria, genetics, kidney