Kidney Week

Abstract: SA-OR077

Randomized Controlled Phase 2 Study to Evaluate Iptacopan in Participants with Active ANCA-Associated Vasculitis (AAV): Interim Renal-Focused Results

Session Information

• Late-Breaking Research Orals: Pediatrics, Genetics, and Glomerular Diseases
  October 24, 2026 | Location: Four Seasons Ballroom 2, Convention Center
  Abstract Time: 05:18 PM - 05:30 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Pugnet, Grégory, Toulouse University Hospital, Toulouse, France

Grégory Pugnet, MD, PhD

• Terrier, Benjamin, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Université Paris-Cité, Paris, France

Benjamin Terrier

• Löffler, Christian, Medius Klinik, Kirchheim, Germany

Christian Löffler, DrMed

• Zhao, Zhanzheng, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

Zhanzheng Zhao, MD, PhD

• Magri, Sebastian Juan, Universidad Nacional de la Plata, La Plata, Argentina

Sebastian Juan Magri, PhD

• Brigante, Jorge Alejandro, Sanatorio Guemes, Buenos Aires, Argentina

Jorge Alejandro Brigante, MD, MSc

• Alibaz-Oner, Fatma, Marmara University, Istanbul, Turkey

Fatma Alibaz-Oner, MD

• Jones, Rachel B., Addenbrook's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom

Rachel B. Jones, MD, MBBS

• Chen, Min, Peking University First Hospital, Beijing, China

Min Chen, MD, PhD

• Alvarado, Rodolfo Nicolas, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

Rodolfo Nicolas Alvarado, MD

• Schreiber, Adrian, Charité-Universitätsmedizin Berlin, Berlin, Germany

Adrian Schreiber, DrMed

• Bazsó, Anna, Semmelweis Egyetem, Budapest, Hungary

Anna Bazsó, MD, PhD

• Betrains, Albrecht, UZ Leuven, Leuven, Flanders, Belgium

Albrecht Betrains, MD, PhD

• Muthusamy, Shilpa, Novartis Pharmaceuticals UK Ltd, London, England, United Kingdom

Shilpa Muthusamy, MBBS

• Hanser, Malika, Novartis Pharma AG, Basel, BS, Switzerland

Malika Hanser, PharmD, PhD

• Wagner, Julia, Novartis Pharma AG, Basel, BS, Switzerland

Julia Wagner, PhD

• Ghanshani, Swati, Novartis Healthcare Private Limited Hyderabad, Hyderabad, Telangana, India

Swati Ghanshani, MSc

• Nidamarthy, Prasanna Kumar, Novartis Healthcare Private Limited Hyderabad, Hyderabad, Telangana, India

Prasanna Kumar Nidamarthy

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

Imelda Schuhmann, PhD

• Junge, Guido, Novartis Pharma AG, Basel, BS, Switzerland

Guido Junge, MD, PhD

Background

This study (NCT06388941) evaluates the efficacy, safety and tolerability of iptacopan vs placebo (PBO) in anti-MPO⁺ or anti-PR3⁺ participants (pts) with newly diagnosed or relapsed AAV.

Methods

The study comprises a 24-week (W) double-blind induction period (iptacopan 200mg twice daily vs PBO), each in combination with rituximab [RTX] and protocol-defined glucocorticoid (GC) taper, followed by a 24W open-label maintenance period. In maintenance, only PBO pts receive RTX re-dosing. The primary endpoint is sustained remission through W48, defined as complete remission at W24 (Birmingham Vasculitis Activity Score [BVAS]=0 and GC ≤5mg/day) without major relapse through W48. We present per protocol planned interim results, focusing on renal outcomes and safety at W24.

Results

84 pts with active AAV (63.9% [n=53] with renal involvement on BVAS at baseline [BL]) were randomized 1:1 to receive iptacopan (n=40) or PBO (n=43), with one not treated. There was a 20% decline in UPCR from BL at W4 in the iptacopan arm vs no change with PBO, and a 40% reduction at W24 with iptacopan vs 30% with PBO. At W4 plasma C3a and urine C5a (n=52) were reduced by 65% and 74%, respectively in the iptacopan arm (with minimal change in the PBO arm), correlating with a sustained reduction in UPCR (Figure). BL eGFR (mean 70.3 [iptacopan] and 59.7 [PBO] mL/min/1.73m²) remained stable at W24. Adverse event rates were similar between groups, with low infection rates and 100% adherence to antibiotic prophylaxis.

Conclusion

Iptacopan showed early reduction in UPCR compared to PBO in pts with active AAV. Target engagement was demonstrated by a robust reduction in complement biomarkers. Iptacopan in combination with RTX and GC taper was generally well tolerated, with a safety profile in line with other iptacopan studies.

Acknowledgment

Professional medical writing assistance was provided by Carol Crawford (Novartis Ireland Ltd.) and funded by Novartis Pharma AG.

Ratio to BL of UPCR, plasma C3a and creatinine normalized urine C5a in participants treated with iptacopan or PBO.

Funding

• Commercial Support – Novartis Pharma AG