Kidney Week

Abstract: FR-PO853

Safety and Efficacy of Iptacopan in Patients with IgA Nephropathy with Baseline eGFR 20 to <30 mL/min: Phase 3 APPLAUSE-IgAN Subcohort Results

Session Information

• IgA Nephropathy: Clinical, Outcomes, and Therapeutics
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

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

Dana V. Rizk, MD

• Kollins, Dmitrij, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Dmitrij Kollins, MD, PhD

• Papachristofi, Olympia, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Olympia Papachristofi, MS, MSc, PhD

• Hach, Thomas, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Thomas Hach, MD

• Jacinto-Sanders, Severina, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Severina Jacinto-Sanders, PhD

• Merkel, Tobias, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Tobias Merkel, PhD

• Schmouder, Robert L., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Robert L. Schmouder, MD

• Kulmatycki, Kenneth M., Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States

Kenneth M. Kulmatycki, PhD

• Renfurm, Ronny W., Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Ronny W. Renfurm, MD, MBA

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

Vlado Perkovic, MBBS, PhD, FASN

Background

Treatment of patients (pts) with advanced IgAN and estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² is limited to supportive care. Iptacopan specifically binds Factor B and inhibits the alternative complement pathway (AP), which is involved in IgAN pathogenesis. We present results from the APPLAUSE-IgAN subcohort with baseline eGFR 20-<30 mL/min/1.73 m².

Methods

APPLAUSE-IgAN (NCT04578834), a Phase 3, randomized, double-blind, placebo (pbo)-controlled trial, enrolled adults with biopsy-confirmed IgAN with proteinuria ≥1 g/g despite stable supportive therapy. Pts were randomized 1:1 to iptacopan 200 mg or pbo twice daily for 24 months while remaining on supportive therapy. Safety, efficacy, and pharmacokinetics (PK) of the low baseline eGFR subcohort were descriptively assessed at Month (M) 9 at time of interim analysis (IA).

Results

The analysis included 27 pts (13 iptacopan, 14 pbo) randomized to the low eGFR cohort at time of IA. Baseline demographic and disease characteristics were similar for iptacopan vs pbo: median (IQR) 24h urine protein-creatinine ratio (UPCR) 2.1 (1.7-2.5) vs 1.8 (1.4-2.4) g/g; mean (SD) eGFR 24.7 (2.8) vs 25.8 (2.9) mL/min/1.73m². All pts received maximally approved/tolerated RASi doses. Serious adverse events (AEs) occurred in 2 pts in each arm and AEs leading to treatment discontinuation in 1 pt in each arm. The most frequent AE was COVID-19 (23.1% iptacopan, 35.7% pbo). Proteinuria (24h-UPCR and 24h urine albumin-creatinine ratio) decreased from baseline to M9 in the iptacopan arm but increased in the pbo arm (Table). At M9, the relative reduction in median 24h-UPCR was 34.5% for iptacopan vs pbo, consistent with the primary analysis. PK data will be presented.

Conclusion

In pts with baseline eGFR 20-<30 mL/min/1.73m², iptacopan was well tolerated with a favorable safety profile, and decreased proteinuria vs pbo (34.5% at M9). Iptacopan may therefore represent a potential treatment option for pts with low eGFR.

Funding

• Commercial Support – Novartis Pharma AG