Lower doses of nedosiran show potential for patients with PH1 and severe CKD
Nedosiran, an investigational RNA-interference therapeutic, has shown promising results in a Phase 1 study for the treatment of primary hyperoxaluria (PH), according to a new study.
The study demonstrated that lower doses of nedosiran may provide similar benefits in reducing urinary oxalate levels in patients with PH1 who have advanced kidney disease (CKD Stages 4/5) compared to standard doses in patients with normal kidney function or less severe CKD (Stages 2/3).
In this open-label, single-dose trial, involved 34 participants, 24 had chronic kidney disease (CKD) Stages 4/5, either undergoing hemodialysis (Groups 1a and 1b) or not (Group 2), and 10 had normal kidney function (Group 3). All participants received a single subcutaneous dose of nedosiran sodium at 170 mg.
Those with CKD Stages 4/5 exhibited approximately twice the nedosiran exposure compared to those with normal kidney function. In addition, the timing of hemodialysis in relation to nedosiran administration did not have a significant impact on pharmacokinetics.
The study found that nedosiran was well-tolerated.
Population pharmacokinetic-pharmacodynamic analyses were conducted using data from this study in conjunction with 4 others.
The most promising finding was that lower doses of nedosiran may provide comparable exposure and potentially lead to a reduction in 24-hour urinary oxalate levels in patients with PH1 who have CKD Stages 4/5.
Amrite A, Fuentes E, Marbury TC, Zhang S. Safety, Pharmacokinetics, and Exposure-Response Modeling of Nedosiran in Participants With Severe Chronic Kidney Disease. Clin Pharmacol Drug Dev. 2023;doi: 10.1002/cpdd.1320. Epub ahead of print. PMID: 37605486.