ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: INFO17-TH

ORIGIN 3: Pivotal Ph3 Study Evaluating Effect of Atacicept vs. Placebo on Proteinuria and Renal Function Preservation in IgA Nephropathy (IgAN)

Session Information

  • Informational Posters - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • No subcategory defined


  • Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
  • Maes, Bart D., AZ Delta vzw, Roeselare, West-Vlaanderen, Belgium
  • Israni, Rubeen K., Vera Therapeutics, Inc., Brisbane, California, United States
  • Wei, Xuelian, Vera Therapeutics, Inc., Brisbane, California, United States
  • Floege, Jürgen, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany
  • Jha, Vivekanand, The George Institute for Global Health India, New Delhi, Delhi, India
  • Tesar, Vladimir, Univerzita Karlova, Praha, Czechia
  • Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China
  • Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
  • Suzuki, Hitoshi, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Trimarchi, Hernan, Hospital Britanico de Buenos Aires, Buenos Aires, Federal District, Argentina
  • Lin, Celia J.F., Vera Therapeutics, Inc., Brisbane, California, United States
  • Lafayette, Richard A., Stanford University, Stanford, California, United States

Group or Team Name

  • ORIGIN 3 Study Team

IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide, with up to 50% of patients progressing to ESRD or death within 20 years.1,2 B Lymphocyte Stimulator (BLyS) and A PRoliferation-Inducing Ligand (APRIL) play an important role in the maturation, function and survival of B cells and plasma cells including Ig switching, leading to the elevated serum levels of galactose-deficient IgA1 (Gd-IgA1), anti-Gd-IgA1 autoantibodies, and immune complex formation that are central to IgAN pathogenesis. Atacicept, a dual BLyS/APRIL inhibitor, has been shown to reduce circulating levels of Gd-IgA1, anti-Gd-IgA1, and immune complexes, and is a potential disease-modifying approach to treating IgAN.
Two Ph2 studies (JANUS [NCT02808429] and ORIGIN [NCT04716231]) evaluated safety and efficacy of atacicept vs placebo in IgAN. In ORIGIN, atacicept 150 mg showed placebo-adjusted UPCR reductions of 35% (p=0.012; intent-to-treat analysis) and 43% (p=0.003; prespecified per-protocol analysis) with eGFR stabilization (+1.6% change from baseline vs -8.5% for placebo; p=0.038) at 36w. Safety was comparable between atacicept and placebo.
Study Design (Figure)
ORIGIN 3 is a global, randomized, double-blind, placebo-controlled Ph3 trial evaluating safety and efficacy of atacicept 150 mg for treatment of IgAN. Eligible patients are adults with biopsy-proven IgAN and persistent proteinuria despite stable and maximum-tolerated RASi regimen for ≥12w (see figure for key entry criteria).
376 patients globally will be randomized 1:1 to self-administered subcutaneous atacicept 150 mg or placebo for 104w in a double-blind period, followed by a 52w open-label extension. The primary endpoint is UPCR % change from baseline at 36w analyzed using a mixed-effects model with repeated measurement. The key secondary endpoint is annualized eGFR slope up to 104w.
This pivotal Ph3 study will further evaluate atacicept’s disease-modifying potential as a treatment for IgAN.
1Kwon CS. J Health Econ Outcomes Res 2021
2Pitcher D. Clin J Am Soc Nephrol 2023


  • Vera Therapeutics, Inc.