Understanding Zigakibart's Potential in IgA Nephropathy, with Jonathan Barratt, MD, PhD

The 100-week data from the phase 1/2 ADU-CL-19 trial suggest that zigakibart, an APRIL inhibitor under development by Novartis, offers durable reductions in proteinuria and maintains a favorable safety profile in patients with IgA nephropathy (IgAN).

The phase 1/2 study, launched in 2019, included 40 patients with persistent proteinuria receiving zigakibart every two weeks—initially by IV or subcutaneous injection—and added to maximally tolerated renin–angiotensin system inhibitors.

Presented at the European Renal Association (ERA 2025) Congress, 100-week data demonstrate patients experienced a mean 60% reduction in proteinuria from baseline, with 55% achieving proteinuria below 500 mg and 31% below 300 mg. Additionally, serum IgA and pathogenic Gd-IgA1 levels dropped by 74%, building on earlier 52-week data showing reductions in IgA, IgM, and IgG of 67%, 78%, and 35%, respectively.

In an interview, lead investigator Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester, emphasized that long-term follow-up is essential to understanding the sustained efficacy and safety of anti-APRIL therapies, especially given the risk of disease rebound after treatment discontinuation

“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,” Barratt explained.. “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.”

To learn more about zigakibart and where it might fit into patient algorithms if approved, check out our interview with Barratt:

Relevant disclosures of interest for Barratt included Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos NV, GSK, Novartis, Travere Therapeuetics, and others.

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. 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