Zigakibart 52-Week Data Demonstrate Potential in IgA Nephropathy

Data from a phase 1/2 trial presented at the 61st European Renal Association Congress suggests that zigakibart was well-tolerated through 52 weeks, with results also pointing to potential efficacy benefits.

Presented by Jonathan Barratt, MD, of the University of Leicester, 52-week results of the 4-part trial suggest use of the anti-APRIL monoclonal antibody was not only well-tolerated, but also associated with durable reductions in serum levels of IgA, IgM, and IgG through 52 weeks of treatment among patients with IgA nephropathy.¹

Named ADU-CL-19, the ongoing phase 1/2 trial was launched in 2019 to explore the effects of zigakibart among patients with biopsy-confirmed IgA nephropathy. Per trial protocol, parts 1 and 2 of the trial assessed single and multiple ascending doses of zigakibart in healthy adults. According to data from ERA 24, a total of 40 patients were included in cohorts 1 and 2 for the trial and completed 52 weeks of treatment.^1,2

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.¹

The primary aims of the trial were to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamic effects and effect on proteinuria.¹

Upon analysis, investigators found zigakibart 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. Investigators pointed out infections were the most common treatment-emergent adverse events, were grade 1 or 2 in severity, and experience day 77.5% of patients.¹

Further analysis indicated use of zigakibart was associated with durable reductions in serum levels of IgA, IgM, and IgG of 67%, 78%, 35%, respectively, at 52 weeks among patients with IgA nephropathy. Additionally, assessments of proteinuria revealed zigakibart was associated with a 53% clinically meaningful reduction in proteinuria in the healthy adults from cohorts 1 and 2.¹

For more on the trial, check out our interview with Barratt:

References:

1. Barratt J, Laura Kooienga L, Agha I, et al. One year of zigakibart treatment shows clinically meaningful proteinuria reduction and good tolerability in a Phase 1/2 study of IgA nephropathy. Abstract presented at 61st European Renal Association Congress. Stockholm, Sweden. May 23-26, 2024.
2. Clinicaltrials.gov. Safety and Tolerability of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy (IgAN). Clinicaltrials.gov. April 8, 2019. Accessed May 27, 2024. https://clinicaltrials.gov/study/NCT03945318.