Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy
In an early-phase trial, zigakibart — a monoclonal antibody against APRIL, a driver of IgA nephropathy — was well tolerated and produced a 60% reduction in proteinuria with stable kidney function over 100 weeks, supporting it as a potentially disease-modifying therapy.
Background
IgA nephropathy is driven in part by the cytokine APRIL (TNFSF13), which promotes production of galactose-deficient IgA1. Zigakibart is a humanized IgG4 monoclonal antibody that binds and neutralizes APRIL, targeting an upstream mechanism of the disease.
Study design
An ongoing phase 1/2 trial (NCT03945318) reporting data from 63 healthy volunteers (single IV doses 10–1350 mg or multiple doses 50–450 mg every 2 weeks) and 40 patients with IgA nephropathy treated with zigakibart 600 mg subcutaneously every 2 weeks, with 100-week follow-up.
Key findings
Zigakibart was well tolerated, with no treatment-emergent adverse events leading to discontinuation or death. In healthy volunteers, exposure rose dose-proportionally with durable reductions in free APRIL, IgA, and IgM. In IgA nephropathy patients, proteinuria fell by 60% with sustained eGFR stabilization at week 100, alongside decreased hematuria and rapid, durable reductions in IgA, galactose-deficient IgA1, and IgM.
Clinical implications
By targeting APRIL upstream of pathogenic IgA production, zigakibart shows robust pharmacological activity and meaningful, sustained proteinuria reduction with eGFR stabilization, positioning it as a promising disease-modifying option for IgA nephropathy. Confirmation in the ongoing phase 3 program is awaited.
Category
Research
Source
Kidney International
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