Kidney Week

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

Authors

• Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Jonathan Barratt,

• Maes, Bart D., AZ Delta vzw, Roeselare, West-Vlaanderen, Belgium

Bart D. Maes,

• Israni, Rubeen K., Vera Therapeutics, Inc., Brisbane, California, United States

Rubeen K. Israni,

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

Xuelian Wei,

• Floege, Jürgen, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany

Jürgen Floege,

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

Vivekanand Jha,

• Tesar, Vladimir, Univerzita Karlova, Praha, Czechia

Vladimir Tesar,

• Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China

Hong Zhang,

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

Sean Barbour,

• Suzuki, Hitoshi, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan

Hitoshi Suzuki,

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

Hernan Trimarchi,

• Lin, Celia J.F., Vera Therapeutics, Inc., Brisbane, California, United States

Celia J.F. Lin,

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

Richard A. Lafayette,

Group or Team Name

• ORIGIN 3 Study Team

Description

Background
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.
Rationale
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

Funding

• Vera Therapeutics, Inc.