Population Pharmacokinetic and Pharmacodynamic Modelling and Simulation for Nedosiran Clinical Development and Dose Guidance in Pediatric Patients with Primary Hyperoxaluria Type 1.

ABSTRACT:

Background and objectives

Nedosiran (Rivfloza^®) is an RNA interference (RNAi) therapy approved for individuals aged ≥ 2 years with primary hyperoxaluria type 1 (PH1), a rare autosomal-recessive disorder causing renal failure and systemic oxalosis. Nedosiran silences lactate dehydrogenase (LDH) mRNA in hepatocytes, reducing oxalate levels. This study evaluated the model-informed clinical development of nedosiran to support proposed doses in children aged 2 to < 12 years with PH1.

Methods

A population pharmacokinetic/pharmacodynamic (Pop-PK/PD) model characterizing the plasma concentration-time profile of nedosiran and its effect on the spot urine oxalate-to-creatinine ratio (Uox/Cr) was developed using data from six trials. Simulations assessed spot Uox/Cr reductio

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12414044 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature