Kidney Week

Abstract: TH-PO1257

The ORIGIN 3 Trial: Atacicept in IgA Nephropathy

Session Information

• Late-Breaking Research Posters
  October 22, 2026 | Location: Exhibit Hall A, 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, England, United Kingdom

Jonathan Barratt, MBChB, PhD

• Brenner, Robert M., Vera Therapeutics Inc, Brisbane, California, United States

Robert M. Brenner, MD

• Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada

Sean Barbour, MD, MSc

• Campbell, Kirk N., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Kirk N. Campbell, MD, FASN

• Doan, Tom, Vera Therapeutics Inc, Brisbane, California, United States

Tom Doan

• Eren, Necmi, Kocaeli Universitesi, Körfez, Kocaeli, Turkey

Necmi Eren, MD

• Floege, Jürgen, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, NRW, Germany

Jürgen Floege, MD

• Fordyce, Marshall W., Vera Therapeutics Inc, Brisbane, California, United States

Marshall W. Fordyce, MD

• Jha, Vivekanand, George Institute for Global Health, New Delhi, India

Vivekanand Jha, MD

• Khawaja, Zeeshan, Vera Therapeutics Inc, Brisbane, California, United States

Zeeshan Khawaja, MD, FASN

• Kim, Beom Seok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)

Beom Seok Kim, MD, PhD

• Liew, Adrian, Mount Elizabeth Hospital, Singapore, Singapore

Adrian Liew, MD, MBBS, FASN

• Maes, Bart D., AZ Delta vzw, Roeselare, Flanders, Belgium

Bart D. Maes, MD, PhD

• Pal, Atanu, Institute of Postgraduate Medical Education and Research, Kolkata, WB, India

Atanu Pal, MD, DrMed

• Pecoits-Filho, Roberto, Pontificia Universidad Catolica de Parana, Curitaba, Brazil

Roberto Pecoits-Filho, MD, PhD, FASN

• Phoon, Richard K S, The University of Sydney, Sydney, New South Wales, Australia

Richard K S Phoon, MBBS

• Rizk, Dana V., The University of Alabama at Birmingham, Birmingham, Alabama, United States

Dana V. Rizk, MD

• Suzuki, Hitoshi, Juntendo Daigaku Igakubu Fuzoku Urayasu Byoin, Urayasu, Chiba Prefecture, Japan

Hitoshi Suzuki, MD, PhD

• Tesar, Vladimir, Univerzita Karlova, Prague, Czechia

Vladimir Tesar, MD, PhD, MBA, FASN

• Trimarchi, Hernan, Hospital Britanico de Buenos Aires, Buenos Aires, Argentina

Hernan Trimarchi, MD, PhD, FASN

• Wei, Xuelian, Vera Therapeutics Inc, Brisbane, California, United States

Xuelian Wei, PhD

• Yu, Lixi, Vera Therapeutics Inc, Brisbane, California, United States

Lixi Yu, PhD

• Zhang, Hong, Peking University, Beijing, China

Hong Zhang, MD, PhD

• Lafayette, Richard A., Stanford University, Stanford, California, United States

Richard A. Lafayette, MD

Background

Atacicept is a native human TACI-Fc fusion protein that inhibits B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). In the interim analysis of ORIGIN 3, atacicept achieved statistically significant reduction in urinary protein-to-creatine ratio (UPCR) at Week 36. Following FDA review, atacicept received accelerated approval and alignment was reached on an earlier final efficacy analysis than all patients completing 104 weeks, allowing an earlier transition of placebo-treated patients to open-label atacicept.

Methods

ORIGIN 3 is a multinational, Phase 3, randomized, double-blind, placebo-controlled trial in adults with IgAN. Patients received atacicept 150 mg or placebo self-administered subcutaneously once weekly at home. Prespecified, hierarchical efficacy endpoints included placebo-adjusted change from baseline in estimated glomerular filtration rate (eGFR) at Week 52; annualized eGFR slope through Week 104; serum galactose-deficient immunoglobulin A1 (Gd-IgA1) at Week 52; hematuria resolution at Week 52; and composite kidney-disease progression through Week 104. Safety was assessed.

Results

The 428 randomized patients (214/group) had biopsy-confirmed IgAN and substantial disease burden. Atacicept significantly improved UPCR, Gd-IgA1, and hematuria (Figure 1), with UPCR reductions sustained from Week 52 through Week 104. Placebo-adjusted mean change in eGFR, eGFR annualized slope, and the composite kidney progression endpoint were statistically significant and full results will be presented. Atacicept significantly reduced the risk of composite kidney-disease progression, with 8 placebo patients progressing to dialysis, kidney transplantation, or death vs. 0 atacicept patients. Adverse events occurred in 74.8% of patients receiving atacicept and in 78.0% on placebo. Infection rates were similar (51.4% vs 52.3%); no opportunistic infections or clinically relevant hypogammaglobulinemia occurred.

Conclusion

Atacicept demonstrated statistically significant, concordant improvements across all prespecified efficacy endpoints with a favorable safety profile, supporting its potential as a targeted, disease-modifying therapy.

Figure 1. Atacicept UPCR, Gd-IgA1, and Hematuria Results

Funding

• Commercial Support – Vera Therapeutics, Inc.