Abstract: SA-PO655
Atacicept Reduces Serum Immune Complex Levels in Patients With IgA Nephropathy (IgAN)
Session Information
- Glomerular Diseases: IgA and Complement-Mediated GN
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1302 Glomerular Diseases: Immunology and Inflammation
Authors
- Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
- Lin, Celia J.F., Vera Therapeutics, Inc, Brisbane, California, United States
- Nawaz, Nadia, University of Leicester, Leicester, Leicestershire, United Kingdom
- Molyneux, Karen, University of Leicester, Leicester, Leicestershire, United Kingdom
- Appel, Gerald B., Columbia University Medical Center, New York, New York, United States
- Tumlin, James A., Emory University School of Medicine, Atlanta, Georgia, United States
- Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
Background
IgAN is an autoimmune disease thought to have a multi-hit mechanism in the inflammatory pathogenic process. Elevated serum Gd-IgA1, which plays a central role in IgAN pathogenesis is the first hit. The second hit is the antibodies that develop against Gd-IgA1 (anti-Gd IgA1) leading to formation of immune complexes (third hit). These circulating immune complexes can then deposit in the kidney and cause injury (fourth hit). The Ph2a JANUS, a randomized placebo-controlled clinical trial, showed that atacicept was the first therapeutic to decrease both circulatory Gd-IgA1 and anti-GdIgA1. This analysis investigates whether atacicept can also reduce serum immune complex levels.
Methods
JANUS patients were evaluated for serum IgA-IgG immune complex levels by ELISA at baseline, weeks 4, 12, 24, 48, and 72. Serum samples were normalized using 3 standard serum samples included on all plates.
Results
Decrease in serum IgA-IgG immune complex levels was observed in both atacicept 25 mg and 75 mg groups over time. At 24 weeks, mean percent change from baseline was 17% decrease for atacicept 25 mg, 21% decrease for atacicept 75 mg, and 3% decrease for placebo. At 72 weeks, 29% decrease for atacicept 25 mg, 26% decrease for atacicept 75 mg, and 13% decrease for placebo was observed.
Conclusion
Atacicept is the first therapeutic to show reduction in serum Gd-IgA1, anti-Gd-IgA1, and now immune complex levels in IgAN patients. Atacicept’s ability to mitigate all of the first three hits of the multi-hit hypothesis illustrates its potential to modify the disease. The ongoing Ph2b ORIGIN trial evaluating up to atacicept 150 mg in IgAN pts, will help determine how reduction of these multiple hits translate to renal function.
Funding
- Commercial Support –