#USA #Vienna #IgA nephropathy #zigakibart #APRIL antibody

Long-Term Study on Zigakibart's Efficacy in IgA Nephropathy Patients

A recent analysis of 100-week data from the ongoing Phase 1/2 study of zigakibart, an experimental monoclonal anti-APRIL antibody, suggests its significant potential as a disease-modifying treatment for IgA nephropathy (IgAN). Presented at the 62nd ERA Congress, these findings highlighted lasting remission of proteinuria, stable kidney function, and a reassuring safety profile.

IgAN is the most common type of glomerular disease worldwide and a leading cause of chronic kidney disease. This condition is marked by inflammation and progressive kidney damage, often leading to kidney failure. Alarmingly, many individuals are unaware they have this disease until substantial kidney impairment has occurred, and approximately 50% of IgAN patients may ultimately experience kidney failure.

Zigakibart addresses one of the primary pathways driving disease progression by targeting the APRIL signaling pathway and decreasing the production of pathogenic galactose-deficient IgA1. Professor Jonathan Barratt, the lead investigator, noted, "Zigakibart was developed to disrupt the triggering factor in IgAN pathogenesis, offering a new approach that can halt or significantly delay disease progression."

The ADU-CL-19 study involved 40 adults with biopsy-confirmed IgAN and persistent proteinuria despite consistent supportive therapy. Patients received zigakibart as an intravenous infusion or subcutaneous injection every two weeks, alongside the maximum tolerable doses of Renin-Angiotensin System inhibitors (RASi). The results indicate an effectiveness that surpasses standard treatments.

By week 100, proteinuria had reduced by 60% compared to the baseline. More than half of the patients (55%) achieved levels below 500 mg/24 hours, while 31% reached under 300 mg/24 hours, signaling a deeper remission. The estimated glomerular filtration rate (eGFR) remained stable across all subgroups. "Especially encouraging is the consistency of eGFR stabilization over 100 weeks, even across various proteinuria response groups," emphasized Professor Barratt.

Moreover, treatment led to a consistent reduction in serum immunoglobulins, including a 74% drop in IgA levels and pathogenic Gd-IgA1, confirming the inhibition of the APRIL signaling pathway.

Zigakibart has been well tolerated overall. Most adverse events reported were mild or moderate, with no treatment-related severe infections or discontinuations noted. Infections were the most common serious adverse reactions; however, the study coincided with a high prevalence of COVID-19.

Notably, this represents the longest duration of eGFR stabilization reported for an anti-APRIL agent in IgAN to date. Professor Barratt remarked, "These long-term results reinforce confidence in zigakibart as a potential cornerstone therapy for IgAN. We are eager to see how the upcoming Phase 3 studies will further define its role."

Zigakibart is currently under investigation in a broader population through the global Phase 3 BEYOND study, focusing on primary proteinuria endpoints at 40 weeks, as well as long-term kidney function assessments at 104 weeks. The implications of this ongoing research could change the landscape of treatment for IgAN, offering hope for patients grappling with this challenging condition.