Kidney Week

Abstract: SA-OR66

Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: 12-Month Results from the Phase 3 APPEAR-C3G Study

Session Information

• Glomerular Diseases: Clinical Advances
  October 26, 2024 | Location: Room 6D, Convention Center
  Abstract Time: 04:50 PM - 05:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Nester, Carla M., The University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, United States

Carla M. Nester, MD, MS, FASN

• Smith, Richard J., The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, United States

Richard J. Smith, MD

• Kavanagh, David, Newcastle University, Newcastle upon Tyne, United Kingdom

David Kavanagh, MBChB, PhD

• Vivarelli, Marina, Ospedale Pediatrico Bambino Gesu, Roma, Italy

Marina Vivarelli, MD

• Remuzzi, Giuseppe, IRCCS Istituto di Ricerche Farmacologiche Mario Negri Centro Anna Maria Astori, Bergamo, Lombardia, Italy

Giuseppe Remuzzi, MD

• Zhao, Ming-Hui, Peking Union Medical College Hospital, Beijing, China

Ming-Hui Zhao, MD, PhD

• Wong, Edwin Kwan Soon, Newcastle University, Newcastle upon Tyne, United Kingdom

Edwin Kwan Soon Wong, MBChB, PhD

• Wang, Yaqin, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Yaqin Wang, PhD

• Trapani, Angelo J., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Angelo J. Trapani, PhD

• Krishnan, Induja, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Induja Krishnan, MBBS, MPH

• Webb, Nicholas J., Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Nicholas J. Webb, MD, MBBS

• Meier, Matthias, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Matthias Meier, MD, PhD, FASN

• Bomback, Andrew S., Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States

Andrew S. Bomback, MD, MPH

Background

The Phase 3 APPEAR-C3G study evaluated the efficacy, safety, and tolerability of iptacopan vs placebo in C3G patients (pts).

Methods

APPEAR-C3G (NCT04817618) was a multicenter, randomized, double-blind, placebo-controlled, pivotal Phase 3 study that included adult pts with biopsy confirmed C3G. The study comprised a 6 month (m) randomized double-blinded treatment with iptacopan 200mg bid. vs. placebo followed by 6m open-label iptacopan treatment, as previously described.¹

Results

74 pts were randomized 1:1 to either iptacopan (n=38) or placebo (n=36). Baseline pt demographics were generally balanced; the iptacopan arm exhibited a more severe disease phenotype. 43 (58.1%) pts in the iptacopan (n=22) and placebo (n=21) arms completed 12m treatment at data cut-off (when all pts completed 6m of treatment). The study met its primary endpoint, demonstrating a statistically significant reduction in 24h UPCR with iptacopan treatment at 6m (35.1%, 1-sided p=0.0014, 95% CI:13.8%, 51.1%) vs. placebo, sustained up to 12m (Figure). Iptacopan showed a sustained improvement in pts meeting the composite renal endpoint (≥50% reduction UPCR + ≤15% reduction in eGFR at 12m), 43.5% (iptacopan vs. placebo) and 25.0% (switched to iptacopan). Iptacopan led to improvements in the trajectory of eGFR compared to pts’ historical eGFR decline. Iptacopan demonstrated a favorable safety profile with no new safety signals identified. Other 12m primary and key secondary endpoints will be presented.

Conclusion

Iptacopan demonstrated a significant and clinically meaningful proteinuria reduction on top of supportive care at 6m in the APPEAR-C3G study; sustained up to 12m. Iptacopan was well tolerated with a favorable safety profile in C3G pts.


Reference: 1. Bomback AS, et al. Kidney Int Rep. 2022;7:2150–9

Funding

• Commercial Support – Novartis Pharma AG