Kidney Week

Abstract: FR-OR065

Effect of Iptacopan on Complement and Inflammatory Biomarkers in IgAN: Final 24-Month Results of the Phase 3 APPLAUSE-IgAN Study

Session Information

• New IgAN Therapies: Subgroups, Outcomes, and Biomarkers
  October 23, 2026 | Location: Room 501, Convention Center
  Abstract Time: 04:40 PM - 04:50 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

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

Dana V. Rizk, MD

• Perkovic, Vlado, University of New South Wales, Sydney, New South Wales, Australia

Vlado Perkovic, MBBS, PhD, FASN

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

Jonathan Barratt, MBChB, PhD

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

Hernan Trimarchi, MD, PhD, FASN

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

Bart D. Maes, MD, PhD

• Kashihara, Naoki, Kawasaki Ika Daigaku, Kurashiki, Okayama Prefecture, Japan

Naoki Kashihara, MD, PhD

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

Hong Zhang, MD

• Agarwal, Shiuli, Novartis Pharma AG, Basel, BS, Switzerland

Shiuli Agarwal, PhD

• Schuhmann, Imelda, Novartis Pharma AG, Basel, BS, Switzerland

Imelda Schuhmann, PhD

• Coomar, Dyuti, Novartis Pharma AG, Basel, BS, Switzerland

Dyuti Coomar, MSc, PhD

• Govan, Lindsay, Novartis Pharma AG, Basel, BS, Switzerland

Lindsay Govan, PhD

• Gardenal, Emanuela, Novartis Pharma AG, Basel, BS, Switzerland

Emanuela Gardenal, MSc, PhD

• Hach, Thomas, Novartis Pharma AG, Basel, BS, Switzerland

Thomas Hach, MD

• Desai, Manasi Mital, Novartis Pharma AG, Basel, BS, Switzerland

Manasi Mital Desai, MS, MSc

• Rovin, Brad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad Rovin, MD, FASN

Background

Alternative complement pathway (AP) overactivation is a key contributor to glomerular inflammation and disease progression in patients with IgAN. Iptacopan is a potent, oral, factor B inhibitor that targets the AP. In APPLAUSE-IgAN, iptacopan demonstrated a statistically significant and clinically meaningful improvement in eGFR slope and sustained reductions in proteinuria and hematuria at Month (M) 24, compared to placebo. Here, we present exploratory biomarker results from M24 and from the interim analysis (IA) at M9.

Methods

APPLAUSE-IgAN (NCT04578834), a Phase 3, randomized, double-blind, placebo-controlled trial, enrolled adults with biopsy-confirmed IgAN and proteinuria ≥1 g/g despite optimized supportive treatment. Patients (N=477) were randomized 1:1 to iptacopan 200 mg or placebo twice daily for 24 months while remaining on supportive therapy. Exploratory endpoints included changes from baseline in complement biomarkers (urinary sC5b-9, serum Wieslab activity, C3, and C4). Changes in Gd-IgA1 and in urinary sCD163, a biomarker of intrarenal inflammation, in the IA population at M9 were also evaluated.

Results

At M24, iptacopan reduced Wieslab activity and urinary sC5b-9, increased serum C3, while C4 levels were unchanged, consistent with findings at M9 (Fig. 1A). Levels of Gd-IgA1 remained generally unchanged from baseline in the iptacopan arm, whereas the reduction in sCD163 from baseline was greater with iptacopan compared to placebo (Fig. 1B).

Conclusion

Sustained modulation of complement biomarkers at M9 and M24 indicates that iptacopan selectively and durably inhibits the AP. As expected from iptacopan’s proposed mechanism of action, Gd-IgA1 was not affected. The reduction in urinary sCD163 suggests that iptacopan also attenuates glomerular inflammation in patients with IgAN.

Funding

• Commercial Support – Novartis Pharma AG