Dados do Trabalho

Título

LUMASIRAN FOR PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1 AND IMPAIRED KIDNEY FUNCTION: 12-MONTH ANALYSIS OF THE PHASE 3 ILLUMINATE-C TRIAL

Introdução

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by hepatic oxalate overproduction leading to progressive kidney disease. In PH1, plasma oxalate (POx) increases as kidney function declines; in CKD 3b–5, POx is typically elevated and is associated with an increased risk of systemic oxalosis, making it a relevant trial endpoint. In the ILLUMINATE-C 6-month (M) primary analysis, administration of lumasiran, an RNA interference therapeutic designed to reduce hepatic oxalate production, produced substantial POx reductions and acceptable safety in PH1 patients with impaired kidney function. Here we present 12M results.

Material e Método

ILLUMINATE-C (NCT04152200) is an ongoing Phase 3, single-arm study (Cohort A: N=6, no hemodialysis [HD] at study start; Cohort B: N=15, on HD). The primary analysis period is followed by an extension period (EP) of up to 54M. Key inclusion criteria included genetically confirmed PH1, eGFR ≤45 mL/min/1.73m2, and POx ≥20 μmol/L.

Resultados

All 21 patients entered the EP (median [range] exposure, 14.2 [8.3‒19.7] M). As of the M12 assessments, 2 Cohort A patients (baseline eGFR, 8.6‒16.0 mL/min/1.73m2) initiated HD. In Cohort B, 1 patient received a kidney transplant, discontinued HD, and continued lumasiran; 1 received a liver/kidney transplant and discontinued lumasiran. POx mean % reduction from baseline at M12 was 69.3% and 34.3% in Cohorts A and B, respectively; mean absolute reduction was 60.7 and 42.4 µmol/L. POx AUC0‒24h mean % reduction from baseline between HD sessions was 40.9% at M12 (Cohort B). Most burdensome symptoms improved or remained stable with lumasiran. The most common lumasiran-related adverse events (AEs) were mild, transient injection-site reactions. There were no deaths or lumasiran-related serious or severe AEs, discontinuations, or withdrawals.

Discussão e Conclusões

Lumasiran showed sustained POx reductions in PH1 patients with CKD 3b–5, with an acceptable safety profile through M12. The impact on systemic oxalosis and transplant outcomes will be further monitored in the EP.

Palavras Chave

Genetic Diseases, Kidney