POS-038 ALTERNATIVE COMPLEMENT PATHWAY INHIBITION WITH IPTACOPAN TO ARREST DISEASE PROGRESSION IN C3 GLOMERULOPATHY (APPEAR-C3G): A PHASE 3 STUDY

IntroductionComplement 3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway (AP) of the complement system. Around 50% of patients progress to kidney failure within 10 years of diagnosis. Currently, there are no approved therapies for C3G. Iptacopan (LNP023) is an oral, first-in-class, potent and selective inhibitor of factor B, a key regulator of the AP. In a previously reported phase 2 study, 12 weeks treatment with iptacopan was associated with 45% reduction in proteinuria (p=0.0003), stabilization of eGFR in native kidneys of C3G patients and reduction in C3 deposit scores on renal biopsy in patients with recurrent C3G after transplantation (p=0.03). Iptacopan showed a favorable safety and tolerability profile in both cohorts.MethodsResultsRecruitment ongoing.ConclusionsThis Phase 3 study will provide valuable evidence towards the efficacy and safety of iptacopan in C3G patients with native kidney disease.Conflict of interest Corporate sponsored research or other substantive relationships:Richard JH Smith: research funding from NIH, consultant for Novartis. David G Kavanagh: grant support from Medical Research Council Wellcome Trust Kidney Research UK Complement UK Fight For Sight, Macular Society, consultant for Silence Therapeutics, Alexion Pharmaceuticals, Novartis, Apellis and Sarepta, Founder and Scientific Advisor, Gyroscope Therapeutics, Advisory board involvement includes Novartis, Sarepta Gyroscope Therapeutics, Silence Therapeutics. Ronda Tawfik, Angelo J Trapani, Yaqin Wang, Nicholas Webb and Matthias Meier are employees and stockholders of Novartis. Marina Vivarelli: honoraria for advisory boards and consulting fees, participation in clinical studies sponsored by the following pharmaceutical companies: Achillion Alexion Apellis Bayer Catalyst Novartis Roche Retrophin/Travere. Andrew S Bomback: consulting honoraria from Achillion, Alexion, Chemocentryx, Novartis, Silence, Catalyst, and Principio. IntroductionComplement 3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway (AP) of the complement system. Around 50% of patients progress to kidney failure within 10 years of diagnosis. Currently, there are no approved therapies for C3G. Iptacopan (LNP023) is an oral, first-in-class, potent and selective inhibitor of factor B, a key regulator of the AP. In a previously reported phase 2 study, 12 weeks treatment with iptacopan was associated with 45% reduction in proteinuria (p=0.0003), stabilization of eGFR in native kidneys of C3G patients and reduction in C3 deposit scores on renal biopsy in patients with recurrent C3G after transplantation (p=0.03). Iptacopan showed a favorable safety and tolerability profile in both cohorts.