Abstract: INFO12-TH
ORIGIN Extend: A Long-Term Extension Study of Atacicept in IgAN
Session Information
- Informational Posters - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Lafayette, Richard A., Stanford University School of Medicine, Stanford, California, United States
- Brenner, Robert M., Vera Therapeutics Inc, Brisbane, California, United States
- Yin, Mengya, Vera Therapeutics Inc, Brisbane, California, United States
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
Group or Team Name
- ORIGIN Extend Study Team.
Description
Background
IgA nephropathy (IgAN) is a B-cell mediated kidney disease predominantly diagnosed in young adults. Within 10-20 years of diagnosis ≥50% of patients with IgAN will develop kidney failure. B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) bind the TACI receptor on B cells and play key roles in IgAN pathophysiology by fueling B cells to produce galactose-deficient IgA1 (Gd-IgA1) and anti-Gd-IgA1 autoantibodies. These form immune complexes which drive clinical disease. Atacicept, a native human TACI-Fc fusion protein, binds BAFF and APRIL with nanomolar affinity to modulate dysregulated B cell activity and has been shown to reduce circulating levels of Gd-IgA1 and immune complexes.
The ORIGIN2b study evaluated safety and efficacy of atacicept in participants (pts) with IgAN and met the primary endpoint with statistically significant and clinically meaningful UPCR reduction. In the open-label extension (OLE), atacicept demonstrated further Gd-IgA1 reductions, hematuria improvement, and UPCR reduction with eGFR stabilization at the rate of decline similar to the general population without kidney disease through 96 wks, suggesting atacicept offers a potentially safe, long-term, disease modifying treatment for IgAN.1 ORIGIN3 is an ongoing global, randomized, double-blind, Phase 3 study of atacicept 150 mg or placebo for 104 wks followed by a 52 wk OLE. The ORIGIN3 study design, patient population, and atacicept dose and subcutaneous (SC) formulation are consistent with ORIGIN2b study. Here, we describe an OLE trial developed to ensure continued access to atacicept for study pts.
Study Design
ORIGIN Extend is a global, multicenter Phase 2 study to assess long-term safety, tolerability, and efficacy of atacicept 150 mg for treatment of IgAN. Eligible pts will have completed the protocol-defined treatment period in the ORIGIN2b or ORIGIN3 clinical trials. Pts will receive atacicept 150 mg SC weekly injections, self-administered at home for up to 3 years. Key efficacy and safety endpoints include changes in serum Gd-IgA1 levels, hematuria, proteinuria, and eGFR. ORIGIN Extend will provide pts continued access to atacicept, capture longer-term safety and efficacy data, and explore reinitiation of atacicept following an off-treatment period.
1Barratt J. JASN 2024.
Funding
- Vera Therapeutics, Inc