Kidney Week

Abstract: INFO13-FR

Evaluation of Pathophysiology Biomarkers in Kidney Biopsies Collected in IMAgINATION, A Phase 3 Study of Sefaxersen in Patients with IgAN

Session Information

• Informational Posters - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• No subcategory defined

Authors

• Barratt, Jonathan, University of Leicester College of Life Sciences, Leicester, England, United Kingdom

Jonathan Barratt, MBChB, PhD

• Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy

Loreto Gesualdo, DrMed

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

Dana V. Rizk, MD

• Li, Hua, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China

Hua Li, MD

• Noronha, Irene L., Universidade de Sao Paulo, São Paulo, SP, Brazil

Irene L. Noronha, MD, PhD

• Duggal, Vishal, Genentech Inc, South San Francisco, California, United States

Vishal Duggal, MD

• Schmit, Nadine, F Hoffmann-La Roche AG, Basel, BS, Switzerland

Nadine Schmit, PhD

• Kamath, Nikhil, Roche UK Ltd, Welwyn Garden City, England, United Kingdom

Nikhil Kamath, MD

• Nash, Amanda, Roche UK Ltd, Welwyn Garden City, England, United Kingdom

Amanda Nash, MSc

• Sasenarine, Roop Naron, Hoffmann-La Roche Limited, Mississauga, Ontario, Canada

Roop Naron Sasenarine, MLA

• Liu, Chang, Roche Holdings Inc, Shanghai, China

Chang Liu

• Lo, Jeannette, Genentech Inc, South San Francisco, California, United States

Jeannette Lo, PhD, MPH

Description

Introduction: The complement alternative pathway (AP) has been implicated in the pathogenesis of IgA nephropathy (IgAN) and increased activity of Factor B (FB), a key mediator of the AP, is associated with poorer kidney outcomes^1,2. Mesangial deposition of IgA and complement, including AP proteins, is often observed in the diagnostic biopsy but there is limited understanding of in situ changes during disease progression or treatment^3-5. Sefaxersen (RO7434656, IONIS-FB-LRx), an antisense oligonucleotide (ASO) against FB, is the first AP mRNA-targeting therapy in late-stage development for the treatment of IgAN⁶. We previously reported reductions in AP activity and urine protein to creatinine ratio (UPCR) in a Phase 2 IgAN study of sefaxersen (NCT04014335)⁷.

Methods: IMAgINATION (NCT05797610) is a Phase 3, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of sefaxersen in adults with biopsy-confirmed primary IgAN. The primary endpoint is a change from baseline in 24h UPCR at Week 37. Key secondary endpoints include eGFR slope from baseline at Week 105, time to the composite kidney failure endpoint and patient-reported outcomes. In addition to blood and urine biomarkers, optional kidney biopsy samples will be collected at baseline, Week 37, and Week 105 for histopathology assessments including MEST-C score, complement and immune complex deposition, and exploratory biomarkers of inflammation and fibrosis.

Results: Characterization of baseline and post-treatment kidney tissue biomarkers and their concordance with blood/urine biomarkers and disease progression are expected upon study completion.

Conclusions: The assessment of blood, urine and tissue pathophysiology biomarkers in the placebo-controlled IMAgINATION study of sefaxersen may uniquely support the understanding of systemic and in situ drug mechanism of action, disease modification, and association with disease progression in patients with IgAN.

Funding

• Roche