#4057 SUPERIOR PROTEINURIA REDUCTION WITH SPARSENTAN IN IMMUNOGLOBULIN A NEPHROPATHY (IGAN): A PROTECT STUDY INTERIM ANALYSIS

Abstract Background and Aims IgAN is the most common glomerular disease worldwide. Despite optimized standard of care, patients with progress to kidney failure within 10-15 years, consequently seriously affecting their quality life mortality. Treatments that reduce proteinuria risk progression are urgently needed for IgAN. Sparsentan a novel, oral, non-immunosuppressive, single molecule dual endothelin angiotensin receptor antagonist being investigated focal segmental glomerulosclerosis. The Phase 3 PROTECT study examining long-term antiproteinuric nephroprotective potential safety sparsentan compared an active control, blocker (ARB) irbesartan, in adults Reported here pre-specified interim primary efficacy endpoint outcomes. Method ongoing, global, 3, multicenter, randomized, double-blind, controlled designed evaluate versus control irbesartan overt despite receiving maximized treatment converting enzyme inhibitor (ACEi) and/or ARB. duration 270 weeks; double-blind period 114 weeks (110 4 follow-up) open-label extension up 156 weeks. Adult biopsy-proven (excluding secondary another condition or IgA vasculitis), urine protein excretion value ≥1.0 g/day, eGFR ≥30 mL/min/1.73m2, systolic/diastolic blood pressure ≤150/≤100 mmHg, on stable dose ACEi ARB therapy at least 12 prior screening both patient's maximum tolerated one-half labeled were eligible inclusion. Patients took last day before randomization. randomized 1:1 (target 400 300 mg/day, respectively), stratified by values. change from baseline protein/creatinine ratio (UP/C, based 24-hour sample) Week 36 was analyzed using mixed model repeated measures analysis. evaluation included assessment emergent adverse events. Results A total 671 screened; 406 clinical sites 18 countries, including North America, Europe, Asia Pacific, met eligibility criteria enrolled into PROTECT. Two withdrew initiating treatment. 404 who received drug analysis population. mean reduction UP/C significantly greater (-49.8%) (-15.1%, P<0.0001). Proteinuria consistency across demographic characteristics rates complete partial remission reported, as well sustained over time. Safety outcomes related edema liver function tests reported. Overall, generally well-tolerated comparable irbesartan. Conclusion results show adult persistent above 1 g/day treated ACEis ARBs, once-daily head-to-head labelled produced robust clinically meaningful proteinuria. consistent previous studies FSGS