Abstract: TH-OR083
ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN
Session Information
- Opening Plenary: ASN President's Address, State-of-the-Art Lecture, Featured High-Impact Clinical Trials
November 06, 2025 | Location: Hall A, Convention Center
Abstract Time: 09:02 AM - 09:14 AM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
- Brenner, Robert M., Vera Therapeutics Inc, Brisbane, California, United States
- Campbell, Kirk N., University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Doan, Tom, Vera Therapeutics Inc, Brisbane, California, United States
- Eren, Necmi, Kocaeli Universitesi, Körfez, Kocaeli, Turkey
- Floege, Jürgen, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, NRW, Germany
- Jha, Vivekanand, The George Institute for Global Health India, New Delhi, DL, India
- Kim, Beom Seok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Liew, Adrian, Mount Elizabeth Hospital, Singapore, Singapore
- Maes, Bart D., AZ Delta vzw, Roeselare, Flanders, Belgium
- Pal, Atanu, Institute of Postgraduate Medical Education and Research, Kolkata, WB, India
- Pecoits-Filho, Roberto, Pontificia Universidad Catolica de Parana, Curitaba, PR, Brazil
- Phoon, Richard K S, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia
- Rizk, Dana V., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Suzuki, Hitoshi, Juntendo Daigaku Igakubu Fuzoku Urayasu Byoin, Urayasu, Chiba Prefecture, Japan
- Tesar, Vladimir, Univerzita Karlova, Prague, Czechia
- Trimarchi, Hernan, Hospital Britanico de Buenos Aires, Buenos Aires, Argentina
- Wei, Xuelian, Vera Therapeutics Inc, Brisbane, California, United States
- Zhang, Hong, Peking University First Hospital, Beijing, China
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
Group or Team Name
- ORIGIN Phase 3 Trial Investigators.
Background
IgA nephropathy (IgAN) is a B-cell mediated immune complex glomerulonephritis. Atacicept is a native human TACI-Fc fusion protein that binds and inhibits B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), key immunoregulatory cytokines central to the pathophysiology of IgAN, thereby modulating B-cell activity.
Methods
In this ongoing double-blind, placebo-controlled, multinational Phase 3 trial, patients with biopsy-proven IgAN were randomized 1:1 to 150 mg of atacicept, self-administered subcutaneously once weekly at home, or placebo. The primary endpoint was percentage change from baseline (BL) at Week 36 in the urinary protein-to-creatinine ratio (UPCR) from a 24-hour collection. Secondary endpoints of galactose-deficient IgA1 (Gd-IgA1) percentage change from BL, hematuria resolution, and safety were also evaluated.
Results
The interim analysis included 203 patients (atacicept n=106; placebo n=97). At Week 36, atacicept treatment resulted in a 45.7% UPCR reduction from BL vs. a 6.8% reduction with placebo, with a statistically significant 41.8% (95% CI, 28.9%–52.3%; P<0.0001) treatment difference (Figure). Significant improvements were also observed in Gd-IgA1 and hematuria with atacicept (Figure). The incidence of adverse events was similar between both groups, and most were mild or moderate.
Conclusion
Atacicept treatment resulted in a statistically significant proteinuria reduction compared with placebo at Week 36, as well as Gd-IgA1 reduction, hematuria improvement, and a favorable safety profile. The results demonstrate the potential for atacicept to address the underlying pathophysiology of IgAN and provide a targeted, disease-modifying therapy.
Funding
- Commercial Support – Vera Therapeutics, Inc.