Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy

Area of Science:

• Nephrology
• Complement System Biology
• Pharmacology

Background:

• C3 glomerulopathy (C3G) is a rare, progressive kidney disease caused by overactivation of the alternative complement pathway.
• It often leads to kidney failure and transplant recurrence.
• Iptacopan is an oral complement inhibitor targeting factor B to selectively inhibit the alternative pathway.

Purpose of the Study:

• To evaluate the efficacy and safety of iptacopan in adult patients with C3G.
• To assess iptacopan's effect on proteinuria, kidney function, and complement deposition.

Main Methods:

• Phase 2 extension study of 26 adult patients with native kidney C3G (cohort A) or recurrent C3G post-transplant (cohort B).
• Patients received open-label iptacopan.
• Evaluations included 24-hour urine protein-to-creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), and serum C3 levels at 12 months.

Main Results:

• In cohort A, iptacopan led to a 57% reduction in UPCR and improved eGFR by 6.83 ml/min/1.73 m² at 12 months.
• Serum C3 levels increased significantly in both cohorts.
• In cohort B, while proteinuria reduction was modest, serum C3 levels increased significantly, and eGFR remained stable.

Conclusions:

• Iptacopan demonstrated significant clinical benefits in patients with C3G, including reduced proteinuria and improved kidney function.
• The study supports further investigation into long-term iptacopan treatment for C3G.
• Iptacopan offers a potential therapeutic option for this ultra-rare kidney disease.