Kidney Week

Abstract: INFO09-FR

ORIGIN 3: Pivotal Ph3 Study Evaluating Effect of Atacicept vs. Placebo on Proteinuria and Kidney Function Preservation in IgAN

Session Information

• Informational Posters - 2
  October 25, 2024 | 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

Richard A. Lafayette, MD

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

Bart D. Maes, MD, PhD

• Cooper, Kerry, Vera Therapeutics, Inc., Brisbane, California, United States

Kerry Cooper, MD

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

Xuelian Wei

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

Jürgen Floege, MD

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

Vivekanand Jha, MD

• Tesar, Vladimir, Univerzita Karlova, Praha, Czechia

Vladimir Tesar, MD, PhD, MBA, FASN

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

Hong Zhang, MD, PhD

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

Sean Barbour, MD, MS, MSc

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

Hitoshi Suzuki, MD, PhD

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

Hernan Trimarchi, MD, PhD, FASN

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

Jonathan Barratt, MBChB, PhD

Group or Team Name

• ORIGIN 3 Study Team.

Description

Background
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with up to 50% of patients progressing to ESKD or death within 20 years.^1,2 B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) bind to the TACI receptor on B cells and play a crucial role in their maturation, differentiation, and effector function. Dysregulated B cells produce galactose-deficient IgA1 (Gd-IgA1), which anti-Gd-IgA1 autoantibodies recognize as an autoantigen, forming immune complexes central to IgAN pathogenesis. Atacicept, a TACI-Fc fusion protein that binds BAFF and APRIL to modulate dysregulated B cell activity, has been shown to reduce circulating Gd-IgA1, anti-Gd-IgA1, and immune complexes, and is a potential disease-modifying approach to treating IgAN.
Two Ph2 studies (JANUS and ORIGIN) evaluated safety and efficacy of atacicept vs placebo in IgAN. In ORIGIN, atacicept showed eGFR stabilization and reductions in Gd-IgA1, hematuria, and proteinuria at 72wk, with comparable safety to placebo.³ Atacicept has received FDA Breakthrough Therapy Designation for the treatment of IgAN.
Study Design
ORIGIN 3 is a global, randomized, double-blind, placebo-controlled Ph3 trial evaluating safety and efficacy of atacicept 150mg for treatment of IgAN (Figure). Eligible patients are adults with biopsy-proven IgAN and persistent proteinuria despite stable and maximum-tolerated RASi regimen for ≥12wk (see figure for key entry criteria). 376 patients globally will be randomized 1:1 to self-administered subcutaneous atacicept 150mg or placebo for a 104wk double-blind period, followed by a 52wk open-label extension.
The primary endpoint is UPCR % change from baseline at 36wk analyzed using a mixed-effects model with repeated measurement. The key secondary endpoint is eGFR change from baseline at 104wk.
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
³Lafayette R. Nephrol Dial Transplant 2024;abstr 812

Funding

• Vera Therapeutics, Inc.