Kidney Week

Abstract: FR-PO0838

Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: C3G Extension Trial Interim Results from the Phase 3 APPEAR-C3G Patients

Session Information

• Glomerular Clinical Trials: From Data to Impact
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Nester, Carla M., Stead Family Children’s Hospital - University of Iowa, 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 IRCCS Unita Operativa Semplice di Immunogenetica dei Trapianti, Rome, Lazio, Italy

Marina Vivarelli, MD

• Remuzzi, Giuseppe, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Lombardy, Italy

Giuseppe Remuzzi, MD

• Zhao, Ming-Hui, Peking University, Beijing, China

Ming-Hui Zhao, MD, PhD

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

Edwin Kwan Soon Wong, MBChB, PhD

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

Yaqin Wang, PhD

• Israni, Rubeen K., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Rubeen K. Israni, MD, MPH

• Kalluri, Hari Varun, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Hari Varun Kalluri, PharmD, PhD

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

Induja Krishnan, MBBS, MPH

• Grisouard, Jean, Novartis Pharma AG, Basel, BS, Switzerland

Jean Grisouard, PhD

• 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. Upon completion of study treatment at 12m in APPEAR-C3G, participants had the option to continue open-label iptacopan treatment in the C3G extension study (NCT03955445). Here we present the results from the extension study with iptacopan treatment up to 24m.

Results

Of 73 pts completing the 12m treatment, 66 pts entered the extension study. In the iptacopan arm, the geometric mean reduction in first morning void (FMV) UPCR at Month 12 (35.9%), was sustained up to Month 24 (34.2%) compared to baseline (Figure). In the placebo-iptacopan switch arm, the reduction at Month 12 (34.0%) was also sustained up to Month 24 (29.7%). The mean pre-treatment annualized eGFR slope (95%CI) in all pts (n=74) showed rapid decline with −7.22 mL/min/1.73m²/year (−10.10, −4.35). After initiation of iptacopan treatment, there was stabilization of annualized eGFR slope (95%CI) at −0.29 mL/min/1.73m²/year (−3.88, 3.31) assessed over 24 months. Iptacopan demonstrated a favorable safety profile with no new safety signals identified.

Conclusion

Iptacopan demonstrated sustained reduction in proteinuria and stabilization of eGFR slope with treatment up to 24 months among APPEAR-C3G pts who rolled over to the long-term extension study. Iptacopan was well tolerated with a favorable safety profile in C3G pts.

Funding

• Commercial Support – This study is funded by Novartis Pharma AG

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202599z9n79j