Long-Term Results Confirm Safety and Effectiveness of Zigakibart in Treating IgA Nephropathy

Recent extended data from a Phase I/II clinical trial reinforces the potential of zigakibart, an investigational monoclonal antibody targeting the APRIL pathway, as a promising disease-modifying therapy for IgA nephropathy (IgAN). Presented at the 62nd ERA Congress, the 100-week study demonstrated sustained reduction in proteinuria, stable kidney function, and a favorable safety profile.

IgAN is recognized as the most common glomerular disease globally and a leading cause of chronic kidney disease, often progressing silently until significant renal impairment occurs. Approximately half of affected individuals may eventually develop kidney failure. The disease’s pathogenesis involves inflammation driven by abnormal IgA1 production, contributing to kidney damage.

Zigakibart works by inhibiting the APRIL pathway, crucial in the production of pathogenic galactose-deficient IgA1 (Gd-IgA1), thereby addressing a fundamental aspect of disease progression.

In the study, 40 adults with biopsy-confirmed IgAN and persistent proteinuria despite standard supportive care received zigakibart every two weeks via intravenous or subcutaneous infusion, alongside maximally tolerated renin–angiotensin system inhibitors. Results at Week 100 revealed a 60% average reduction in proteinuria from baseline; over half of the patients achieved proteinuria levels below 500 mg/24h, with nearly one-third reaching below 300 mg/24h, indicating deep remission. Estimated glomerular filtration rate (eGFR) remained stable across all groups, highlighting preserved kidney function.

Additionally, treatment led to significant decreases in serum immunoglobulin levels, including a 74% reduction in IgA and Gd-IgA1, confirming the drug’s mechanism of action. The adverse events reported were primarily mild or moderate, with no serious infections or treatment discontinuations—an especially reassuring aspect given the context of concurrent COVID-19 circulation.

These findings mark the longest reported period of eGFR stabilization for an anti-APRIL agent in IgAN, bolstering confidence in zigakibart's potential for long-term disease control. Lead researcher Professor Jonathan Barratt emphasized the encouraging nature of the results and anticipation for further validation in upcoming Phase III trials.

The larger Phase III BEYOND study is currently underway, assessing the drug’s impact on proteinuria and long-term kidney function over 104 weeks in a broader patient population, with an extension trial also in progress.

Source: https://medicalxpress.com/news/2025-06-term-sustained-efficacy-safety-zigakibart.html