Kidney Week

Abstract: SA-PO797

Experience with Iptacopan in Patients with Recurrent Complement 3 Glomerulopathy (C3G): Early Access Program Data

Session Information

• C3G, TMA, MGRS, Amyloidosis, and More
  October 26, 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

• Smeets, Serge, Novartis Pharma AG, Basel, Switzerland

Serge Smeets, PhD

• Ansari, Soudeh, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States

Soudeh Ansari, PhD

• Rizk, Sviatlana, Novartis Pharma AG, Basel, Switzerland

Sviatlana Rizk, PhD

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

Induja Krishnan, MBBS, MPH

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

Nicholas J. Webb, MD, MBBS

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

Matthias Meier, MD, PhD, FASN

Background

C3G is a severe primary glomerulonephritis driven by alternative complement pathway (AP) dysregulation; >50% of patients (pts) progress to kidney failure in <10 years and there is high risk of recurrence after successful kidney transplantation. Iptacopan is an oral proximal complement inhibitor that specifically binds Factor B and inhibits the AP; Phase 2/3 studies have shown efficacy in proteinuria reduction and favorable safety. An early access program (EAP) was initiated in 2018 (NCT05222412) to provide iptacopan for C3G pts (native and recurrent) with progressive renal insufficiency not eligible for any clinical trial who have exhausted all available therapies. We here focus on outcomes in pts with recurrent C3G post transplantation.

Methods

Unsolicited requests submitted to the EAP were approved if meeting eligibility criteria and applicable local laws/regulations. Recurrent C3G had to be biopsy confirmed. Physicians received a 3-month supply of iptacopan (200 mg twice daily). Resupply requests were submitted generally every 3 months and estimated glomerular filtration rate (eGFR) values collected. Adverse events (AEs) were collected by spontaneous reporting. Cutoff for data collection: 27-Feb-2024.

Results

12 pts with recurrent C3G received iptacopan: median age 40 y (17-76); 75% male; median iptacopan treatment duration 214 days (15-1017); baseline mean eGFR 44.4 mL/min/1.73m² (SD 21.6). Analysis comparing eGFR slope post-transplant prior to and after start of iptacopan treatment suggested potential stabilization of kidney function (Figure). 3 pts reported 26 AEs, of which 12 were serious (all judged not related to iptacopan except 1 of bacterial pneumonia).

Conclusion

Following a historic period of eGFR decline post-transplantation without iptacopan treatment, recurrent C3G pts demonstrated potential stabilization of progression with iptacopan treatment. AEs were consistent with the known safety profile of iptacopan; no new safety signals were identified.

Funding

• Commercial Support – Novartis Pharma AG