Significant Long-term Efficacy of Zigakibart for IgA Nephropathy During ERA Congress

Zigakibart Shines in Long-term Study for IgA Nephropathy

Recent revelations presented at the 62nd ERA Congress illustrate that zigakibart, an investigational anti-APRIL monoclonal antibody, holds promising potential for long-term management of IgA nephropathy (IgAN). Spanning 100 weeks, findings from this ongoing Phase 1/2 study confirmed the medication's efficacy, safety, and ability to modify the course of this prevalent kidney disease.

IgAN is ranked as the most common form of glomerular disease globally, often leading to chronic kidney disease and ultimately kidney failure if left unchecked. Many individuals remain oblivious to their condition until significant renal damage has already occurred, and alarming statistics indicate that approximately 50% of IgAN patients progress to renal failure. This stark reality necessitates innovative treatment strategies, and zigakibart represents a vital step forward.

The mechanism behind zigakibart's effectiveness revolves around its capacity to disrupt the APRIL pathway, which is instrumental in decreasing the production of the pathogenic galactose-deficient IgA1 (GD-IgA1). According to Professor Jonathan Barratt, the lead investigator, “Zigakibart is designed to intercept the initiating factor in IgAN pathogenesis, offering a new approach that may halt or significantly delay progression.”

The clinical trial, known as ADU-CL-19, involved 40 adult participants diagnosed with biopsy-confirmed IgAN who exhibited persistent proteinuria despite receiving standard supportive therapies. Patients were administered zigakibart every two weeks, either through intravenous infusion or subcutaneous injection, combined with maximally tolerated renin–angiotensin system inhibitors (RASi) unless they were RASi-intolerant. This dual approach demonstrated efficiency that outstripped standard care alone.

Upon reaching the 100-week mark, the data revealed a 60% reduction in proteinuria from the baseline. An impressive 55% of participants achieved proteinuria levels below 500 mg/24 h, with 31% recording levels below 300 mg/24 h, reflecting deeper remission levels. Additionally, the estimated glomerular filtration rate (eGFR) remained stable across varying response groups, which is a particularly promising outcome. “The consistency of eGFR stabilisation over 100 weeks, even across proteinuria response groups, is particularly encouraging,” Prof. Barratt stated.

Moreover, treatment led to significant decreases in serum immunoglobulins, including a remarkable 74% drop in both IgA and pathogenic GD-IgA1, indicating effective APRIL pathway inhibition.

Throughout the study, zigakibart was well tolerated by participants, with most adverse events categorized as mild or moderate. Notably, there were no treatment-related severe infections or discontinuations. Infections were the most frequent adverse events recorded, though the duration of the study coincided with a period of heightened COVID-19 prevalence.

These long-term results mark the longest duration of eGFR stabilisation reported for an anti-APRIL agent in IgAN to date. “These long-term results build confidence in zigakibart as a potential cornerstone therapy for IgAN,” expressed Prof. Barratt. The excitement regarding its future prospects amplifies as the next phase of research unfolds. Currently, the global Phase 3 BEYOND study is assessing zigakibart among a broader population, with primary proteinuria endpoints set for 40 weeks, alongside long-term kidney function evaluation stretching across 104 weeks.

The findings from the ERA Congress not only fortify the potential of zigakibart in altering the trajectory of IgA nephropathy but also set the stage for further exploration and hope for patients battling this chronic kidney condition.