#None #IgA nephropathy #ERA Congress #zigakibart

Zigakibart: A Potential Breakthrough in IgA Nephropathy Treatment

The recent ERA Congress has brought to light some compelling long-term data concerning zigakibart, an investigational monoclonal anti-APRIL antibody, aimed at treating IgA nephropathy (IgAN). Results from a 100-week Phase 1/2 study fortify the case for zigakibart as a pivotal player in modifying the course of this common kidney ailment, which is a frequent precursor to chronic kidney disease (CKD).

Understanding IgA Nephropathy

IgA nephropathy is the most prevalent form of glomerular disease worldwide, characterized by persistent inflammation that can lead to kidney damage. Alarmingly, around 50% of patients with IgAN can eventually develop renal failure. Many patients are often unaware of their condition until significant kidney damage has occurred, further underscoring the urgent need for effective treatment options.

Study Overview

The clinical trial, titled ADU-CL-19, involved 40 adult participants diagnosed with biopsy-confirmed IgAN. These patients exhibited persistent proteinuria despite maintaining stable supportive treatments. They were administered zigakibart bi-weekly through intravenous infusion or subcutaneous injection, in conjunction with optimally tolerated renin-angiotensin system inhibitors.

Efficacy Results

At the 100-week mark, notable improvements were reported: proteinuria levels decreased by an impressive 60% from baseline values. More than half of the participants (55%) achieved proteinuria levels below 500 mg over 24 hours, while 31% reached levels under 300 mg, indicating significantly deeper remission. Remarkably, the estimated glomerular filtration rate (eGFR) remained stable across all groups, which is particularly encouraging for long-term patient outcomes.

Professor Jonathan Barratt, the principal investigator, highlighted the importance of maintaining a stable eGFR over the study's duration. The long-term nature of these results is validating, suggesting that zigakibart may offer sustained benefits for those affected by IgAN.

Immunoglobulin Reduction

In terms of safety and tolerability, zigakibart demonstrated positive outcomes. Patients experienced lasting reductions in serum immunoglobulins, including a 74% decrease in both IgA and pathogenic Gd-IgA1, consistent with targeted inhibition of the APRIL pathway. The treatment was generally well-tolerated, with most reported side effects classified as mild or moderate. Notably, there were no severe treatment-related infections or treatment discontinuations, despite the trial coinciding with a spike in COVID-19 cases.

Encouraging Future Outlook

The stability observed in eGFR during the 100-week treatment period marks a significant milestone for therapies targeting the APRIL pathway in IgAN management. As Professor Barratt stated, “These long-term results bolster confidence in zigakibart as a potential foundational therapy for IgAN.”

Looking ahead, the global Phase 3 BEYOND study is underway, evaluating zigakibart in a more extensive population, with primary endpoints focusing on proteinuria at 40 weeks and long-term renal function at 104 weeks. The anticipation surrounding this trial underscores the hope for new avenues in patient care within the realm of nephrology.

In summary, the data presented at the ERA Congress heralds a promising future for zigakibart in the management of IgA nephropathy, signifying a step forward in therapeutic options that could profoundly impact patient lives for years to come.