Successful Iptacopan Treatment of a Patient with C3 Glomerulopathy (C3G)

Introduction: C3G is a complex, ultra rare progressive glomerulonephritis with an estimated annual incidence of 1-2 cases per million. The pathogenesis of C3G centers on the overactivation of the alternative complement pathway (AP) as a result of nephritic factors or genetic mutations . There is a high unmet medical need for new therapies to treat C3G. Iptacopan, which has been recently approved by US FDA for C3G (in March 2025) is a proximal complement inhibitor that binds factor B and inhibits the AP. The present clinical case aims to evaluate the clinical efficacy, safety and tolerability of iptacopan in a patient with C3G. Case Description: Female patient of 62 years old was presented to her doctor with anemia (Hb 10.5) and peripheral oedema. She was referred for hematologist's clinical and laboratory estimation , which was unremarkable. Then, patient presented to renal clinic with eGFR 32 mils/min and proteinuria 3300 mg/24 hours. C3 complement was below normal range. Νο other issues from the medical history of the patient were revealed. Kidney biospy was performed and the diagnosis was C3G. After exclusion of possible secondary forms of C3G, iptacopan was provided for our patient by Novartis Pharma AG via Managed Access Program. Four weeks before starting the treatment with iptacopan the patient received meningococcal, pneumococcal and haemophilus influenzae vaccination. Within 3 weeks after starting the treatment with iptacopan( 200 mg twice daily), kidney function of the patient improved (e GFR: 54 mils/min), proteinuria significantly decreased to a level of 654.8 mg/ 24 hours and C3 complement levers returned to normal range. To date, the treatment with iptacopan is continued and is well tolerated with no adverse side effects and it is worth to mention that the patient is under the monotherapy of iptacopan for nearly 6 months. Gradually proteinuria is within normal range (130mg/ 24 hours) and renal function remains stable. Discussion: Our case report opens an interesting therapeutic field for the use of complement blockers for the treatment of C3G. From this point-of view, the current case report , shows that iptacopan is highly effective regarding the reduction of proteinuria and recovery and stabilization of kidney function and is well tolerated. Our case report suggests that even under the 6-month monotherapy, iptacopan may become a promising oral treatment option for C3G.