Abstract: FR-PO0837
Update to the Long-Term Efficacy and Safety of Iptacopan in C3 Glomerulopathy: 39-Month Phase 2 Extension Study Data
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
- Eisenberger, Ute, Department of Nephrology, University Hospital Essen, Essen, Germany
- Karras, Alexandre, Hopital Europeen Georges Pompidou, Paris, Île-de-France, France
- Le Quintrec, Moglie, Centre Hospitalier Universitaire de Montpellier, Montpellier, Occitanie, France
- Lightstone, Liz, Imperial College London, London, England, United Kingdom
- Praga, Manuel, Universidad Complutense de Madrid, Madrid, Community of Madrid, Spain
- Remuzzi, Giuseppe, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Lombardy, Italy
- Soler Romeo, Maria Jose, Hospital Universitari Vall d'Hebron, Barcelona, CT, Spain
- Liu, Junhao, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
- Israni, Rubeen K., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
- Grisouard, Jean, Novartis Pharma AG, Basel, BS, Switzerland
- Krishnan, Induja, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
- Wong, Edwin Kwan Soon, Newcastle University, Newcastle upon Tyne, England, United Kingdom
Background
The Phase (Ph) 2 extension study evaluates the long-term efficacy and safety of iptacopan treatment in patients with C3 glomerulopathy (C3G), an ultra-rare disease. Here we report the 39-month (M) follow-up data.
Methods
Adults with native (Cohort [Co]A) or recurrent C3G post-kidney transplant (CoB) received iptacopan 200mg twice-daily (bid) for at least 12 weeks (W) in the Ph2 study before entering the open-label extension study (NCT03955445). Long-term efficacy was assessed by several renal endpoints (e.g., proteinuria, eGFR). Safety and tolerability of iptacopan was continually monitored.
Results
Of 27 patients completing the 12W Ph2 study, 26 (16 CoA, 10 CoB) entered the extension study for treatment with iptacopan 200mg bid; 21 patients (13 CoA, 8 CoB) completed 39M follow-up (3M Ph2 plus 36M extension).
In CoA, there was a sustained reduction in proteinuria (first morning void [FMV] UPCR) over time with a reduction of 40% from baseline at 39M. Compared to the pre-treatment eGFR slope of -13.4 ml/min/1.73m2/year, the annualized eGFR slope was -2.1 mL/min/1.73m2/year at 39M (CoA) representing an improvement of +11.4 mL/min/1.73m2/year (p=0.0089) following initiation of iptacopan.
In CoB, proteinuria levels (FMV UPCR) were mostly normal at baseline and remained well controlled (<0.4 g/g in the 7 patients with data at 39M) over the study period up to 39M. The mean change in eGFR from baseline was -5.8 mL/min/1.73m2 at 39M in CoB. 6 of 8 patients (75.0%; 95% CI: 40.9, 92.9) had a stable or improved eGFR (defined as ≤10% reduction in eGFR compared to baseline), and 2 patients had an eGFR decline of >10%.
Iptacopan was generally well-tolerated with safety consistent with iptacopan’s known profile.
Conclusion
Long-term iptacopan therapy is associated with a sustained and clinically relevant reduction in proteinuria and an improved eGFR slope in native C3G. A stable eGFR was maintained in a majority of recurrent C3G patients. Iptacopan was well tolerated with a favorable safety profile in both cohorts.
Funding
- Commercial Support – Novartis Pharma AG