Kidney Week

Abstract: FR-PO856

A Phase 1/2 Trial of Zigakibart in IgA Nephropathy

Session Information

• IgA Nephropathy: Clinical, Outcomes, and Therapeutics
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Jonathan Barratt, MBChB, PhD

• Workeneh, Biruh, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States

Biruh Workeneh, MD, FASN

• Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)

Sung Gyun Kim, MD, PhD

• Lee, Eun Young, Soonchunhyang University Cheonan Hospital,, Cheonan, Korea (the Republic of)

Eun Young Lee, MD, PhD

• Lam, Chun, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Chun Lam, MD

• Filbert, Erin L., Chinook Therapeutics Inc, A Novartis Company, Seattle, Washington, United States

Erin L. Filbert, PhD

• Sorensen, Bess, Chinook Therapeutics Inc, A Novartis Company, Seattle, Washington, United States

Bess Sorensen, MS

• Song, Yuanbo, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Yuanbo Song, PhD

• Khawaja, Zeeshan, Chinook Therapeutics Inc, A Novartis Company, Seattle, Washington, United States

Zeeshan Khawaja, MD, FASN

• Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States

Laura Kooienga, MD

Background

IgAN is the leading cause of primary glomerulonephritis with limited treatment options. Zigakibart is a novel investigational, humanized monoclonal antibody that blocks A PRoliferation-Inducing Ligand (APRIL), a cytokine elevated in patients with IgAN, which promotes pathogenic galactose-deficient IgA1 production, leading to inflammation and kidney injury.

Methods

ADU-CL-19 is an ongoing Phase 1/2 trial (NCT03945318) of zigakibart. Part 3 enrolled patients ≥18 years with biopsy-proven IgAN, total urine protein ≥0.5 g/24h or UPCR ≥0.5 g/g, eGFR ≥30 mL/min per 1.73 m², and on stable/optimized dose of RASi for ≥3 months prior to screening (or RASi intolerant). Patients received zigakibart 450 mg Q2W IV, transitioning to 600 mg Q2W SC at ≥24 weeks (Cohort 1) or 600 mg Q2W SC (Cohort 2) for up to 124 weeks. Key objectives include safety, tolerability, immunogenicity, pharmacodynamic effects, and preliminary effects on proteinuria and eGFR.

Results

Overall, 40 patients were enrolled (n=10 [Cohort 1], n=30 [Cohort 2]); median age 38.5 years; 70% male; 60% White and 33% Asian. Zigakibart was well-tolerated with no adverse events (AEs) leading to study drug discontinuation or deaths. AEs were observed in 34 (85%) patients, most commonly infections (78%) of Grade 1 or 2 in severity; one patient experienced Grade 3 infections. One patient experienced infections deemed treatment related. IgA and IgM levels were reduced by 71% and 79% from baseline, respectively, through Week 76, while reduction in IgG was mild to modest (35%). At Week 76, proteinuria, measured as UPCR from a 24h collection, was reduced by 57% from baseline, and eGFR remained stable (Fig. 1A, 1B). Circulating lymphocyte counts remained stable through the study (Fig. 1C, 1D).

Conclusion

Zigakibart was well tolerated and led to sustained, clinically meaningful reductions in proteinuria and eGFR stabilization in patients. The global Phase 3 BEYOND study (NCT05852938) is also evaluating the efficacy and safety of zigakibart in adults with IgAN.

Funding

• Commercial Support – Chinook Therapeutics Inc, A Novartis Company