OBJECTIVES: Primary hyperoxaluria Type 1 (PH1) is a rare genetic disorder characterized by excessive oxalate production leading to recurrent kidney stones, nephrocalcinosis, and kidney damage. Current treatments aim to reduce oxalate production to prevent renal complications. Lumasiran, an RNA interference molecule targeting glycolate oxidase through HAO1 mRNA silencing, has been approved for the treatment of PH1. Nedosiran, an siRNA therapy inhibiting liver lactate dehydrogenase to lower oxalate production, remains under clinical investigation. The objective of this systemic literature review (SLR) was to identify and summarize the efficacy and safety of both therapies in patients with PH1.

METHODS: PubMed^® and Embase^® were systematically searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The population, intervention, comparator, outcome, and study design criteria were used to identify relevant studies.

RESULTS: Of the 73 records identified, five clinical trials from 12 publications were included. Both lumasiran and nedosiran have shown promising efficacy in reducing urinary oxalate (UOx) levels in patients with PH1. In the ILLUMINATE-A trial, lumasiran achieved substantial reductions in 24‑hour UOx levels at 6 months, maintained to 36 months, along with significant decreases in plasma oxalate levels (p < 0.001) and stable renal function. Similarly, in ALN-GO1-001 and NCT02706886 lumasiran was associated with clinically significant reductions in UOx and plasma oxalate levels. For nedosiran, a marked reduction in UOx levels was reported in both PHYOX2 and PHYOX1 trials, with a notable proportion of patients achieving normal or near-normal UOx levels. Both treatments were associated with stable estimated glomerular filtration rate, along with mild adverse events (AEs), primarily injection site reactions and kidney stone-related AEs.

CONCLUSIONS: This SLR demonstrates that lumasiran and nedosiran are effective in lowering UOx levels, improving renal outcomes with favorable safety profiles, thus emphasizing their potential as long-term therapies for PH1.