ERA 2025: Zigakibart Maintains Efficacy Out to 100 Weeks in ADU-CL-19 Trial

New 100-week data from zigakibart, an APRIL inhibitor, suggests the agent provided sustained reductions in proteinuria with a favorable safety profile among patients with IgA nephropathy (IgAN) and elevated proteinuria.

Presented at the 62nd annual European Renal Association (ERA 2025) Congress, new data from the ADU-CL-19 trial offer the greatest insight yet into the potential of zigakibart, which is currently being examined in a phase 3 trial sponsored by Novartis.1,2,3

“Zigakibart is designed to intercept the initiating factor in IgAN pathogenesis, offering a new approach that may halt or significantly delay progression,” explained lead investigator Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester, in a statement.2

Nephrologists, specifically those specializing in glomerular diseases, have found themselves in the midst of a renaissance in recent years, with the field witnessing multiple therapies receive approval for IgAN after decades without an approved therapeutic option. However, despite this advancement, IgAN still represents an area of significant unmet need. Zigakibart was originally developed by Chinook Therapeutics but was acquired by Novartis in August 2023.

The ADU-CL-19 was a phase 1/2 trial launched in 2019. Per trial protocol, cohort 1 received 450 mg of zigakibart administered intravenously every 2 weeks for 24 weeks followed by a transition to 600 mg of zigakibart administered subcutaneously every 2 weeks while cohort 2 received 600 mg of zigakibart subcutaneously every 2 weeks. In part 3 of the study, which is ongoing, patients with IgA nephropathy received zigakibart for up to 124 weeks. According to investigators, the primary aims of the trial were to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamic effects and effect on proteinuria.1,3

Of note, patients received zigakibart every 2 weeks via intravenous infusion or subcutaneous injection, in addition to maximally tolerated renin–angiotensin system inhibitors.1,3

At ERA 2024, Barratt presented safety data from patients who had completed 52 weeks of treatment. These data indicated was well-tolerated among patients included in the trial. Assessments of treatment-emergent adverse events revealed such events occurred among 85% of patients, but none of these events were considered serious or led to study drug discontinuation. Additionally, use of zigakibart was associated with durable reductions in serum levels of IgA, IgM, and IgG of 67%, 78%, 35%, respectively, at 52 weeks.3

At ERA 2025, Barratt presented the 100-week data from the trial, which included 40 patients with IgAN and persistent proteinuria, which demonstrated patients receiving zigakibart experienced a mean proteinuria reduction of 60% from baseline. Additional data highlighted by investigators included 55% of patients achieving proteinuria less than 500 mg and 31% achieving proteinuria less than 300 mg. In the 100-week results, investigators observed a 74% drop in IgA and pathogenic Gd-IgA1.1,2

“So, what we need to know is that any response to an anti-APRIL approach is able to be sustained over time because what I think all of the data is showing us is that when you stop these agents, the disease comes back,” Barrett explained, in an interview with HCPLive. “So, what we need to understand is that you are not going to lose effectiveness of this approach over time and that you aren't seeing any new or unusual safety signals over time. So, the longer the follow up, the better the quality of data, in my view, in terms of answering those questions. I think the data we're presenting of the 100 weeks exposure to zigakibart is important, both from a safety perspective, but also from an efficacy perspective.”

References:

1. Barratt J., Lee E.Y., Kim S.G., et al. (2025). Sustained Long-Term Efficacy and Safety of Zigakibart Over 100 Weeks in Patients with IgA Nephropathy. Presented at ERA Congress; 5 June 2025; Vienna, Austria.

2. European Renal Association. Long-term data show sustained efficacy and safety of zigakibart in patients with IgA nephropathy. EurekAlert! Published June 4, 2025. Accessed June 4, 2025. https://www.eurekalert.org/news-releases/1085995

3. Campbell P. Zigakibart 52-Week Data Demonstrate Potential in IgA Nephropathy. HCP Live. Published May 27, 2024. Accessed June 4, 2025. https://www.hcplive.com/view/zigakibart-52-week-data-demonstrate-potential-in-iga-nephropathy