Zigakibart slows down eGFR decline in IgA nephropathy

Zigakibart is a monoclonal antibody targeting the A-PRoliferation-Inducing Ligand (APRIL), which is involved in the pathogenesis of IgA nephropathy. Phase 1/2 data from the ADU-CL-19 trial showed that zigakibart preserves kidney function in participants with IgA nephropathy.

The ADU-CL-19 trial (NCT03945318) is an ongoing, phase 1/2 trial investigating zigakibart in participants with IgA nephropathy, a total protein excretion of ≥0.5 g/24h or 24-hour urine protein-creatinine ratio ≥0.5 g/g, and an eGFR ≥30 mL/min/1.73 m². The trial enrolled two cohorts: Cohort 1 received intravenous zigakibart 450 mg every 2 weeks. After the new formulation became available (after 24 weeks, participants of this group switched to 600 mg zigakibart subcutaneously administered every 2 weeks. Cohort 2 received subcutaneously administered 600 mg zigakibart every 2 weeks. The primary endpoint was safety and tolerability, and 40 participants were included in the trial [1].

The 24-hour urine protein-creatinine ratio declined over the initial 52 weeks of therapy in both cohorts, reaching a mean -53.4% reduction. “For the treatment of IgA nephropathy, we aspire to maintain kidney function”, explained Prof. Jonathan Barrat (University of Leicester, United Kingdom). Indeed, zigakibart maintained eGFR levels over the first year of treatment in both the overall population of the trial and the individual cohorts. Zigakibart was overall well-tolerated. While adverse events (AEs) were observed, none led to treatment discontinuation or deaths. Most AEs were infectious events (as expected, as the trial was run during the COVID-19 pandemic). However, 7 participants also developed injection site reactions which were considered treatment-related. Only one serious AE was reported (amnesia) which was not considered to be treatment-related and did not lead to study drug discontinuation.

“In this trial, zigakibart reduced proteinuria, preserved kidney function in terms of a stable eGFR over the 52-week study period, and presented with an acceptable safety profile”, said Prof. Barrat. "We are currently evaluating zigakibart in the BEYOND phase 3 study (NCT05852938) which is open and recruiting”.

1. Barrat J, et al. One year of zigakibart treatment shows clinically meaningful proteinuria reductioon and good tolerability in a Phase 1/2 study of IgA nephropathy. Abstract #55, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024