Abstract: SA-PO0642
Emerging Targeted Therapies in IgAN: A Systematic Review Without Meta-Analysis (SWiM) of Phase 3 Randomized Controlled Trials
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Bouzed, Mohamed, Tripoli University, Tripoli, Libya
- Bouzed, Alla, Tripoli University, Tripoli, Libya
- Mohammed, Khalid M.G, Tanta University, Tanta, Gharbia Governorate, Egypt
- Mohamed, Muner, Ochsner Health, New Orleans, Louisiana, United States
Group or Team Name
- Ochsner Nephrology
Background
IgA nephropathy (IgAN) is a chronic glomerular disease with a long-term risk of progression to kidney failure despite optimized standard care, underscoring the need for disease-modifying therapies. Multiple recent phase 3 randomized trials have evaluated therapies targeting mucosal immunity, complement activation, and endothelin pathways in IgAN.
Methods
We searched PubMed, Cochrane, and ClinicalTrials.gov through April 2026 for phase 3 RCTs of targeted therapies in adults with biopsy-proven IgAN and persistent proteinuria despite optimized renin–angiotensin system blockade.
Outcomes: proteinuria reduction, eGFR slope, and safety.
A meta-analysis was not performed due to study heterogeneity.
Results
Five phase 3 RCTs were identified: NefIgArd (nefecon, n=364), VISIONARY (sibeprenlimab, n=510), APPLAUSE IgAN (iptacopan, n=443), ALIGN (atrasentan, n=340), and PROTECT (sparsentan, n=404). All treatments reduced UPCR versus control groups: 27% for Nefecon at 9 months, 51.2% for sibeprenlimab at 9 months, 38.3% iptacopan at 9 months, 36.1% for atrasentan at 36 weeks, and 41% for sparsentan at 36 weeks (all 95% confidence intervals exclude zero). Kidney function outcomes were heterogeneous in slope definitions, follow-up durations, and comparators. Nefecon demonstrated reduced 2-year eGFR decline versus placebo (2.95 mL/min/1.73m2/yr). Iptacopan demonstrated reduced eGFR decline versus placebo at 2-year follow-up (3.0 mL/min/1.73m2/yr). Sparsentan was associated with reduction in chronic eGFR slope versus irbesartan (1.1 mL/min/1.73m2/yr), although total slope did not reach statistical significance. Atrasentan showed favorable but non-significant effects on kidney function endpoints (p=0.057). Sibeprenlimab kidney function data remain pending.
Safety profiles were consistent with known class-related adverse effects, including edema, blood pressure changes, and infections.
Conclusion
The five phase 3 RCTs of targeted therapies in IgAN demonstrated reductions in proteinuria and, in several trials, slowing of eGFR decline, supporting potential disease-modifying effects. However, interpretation is limited by reliance on surrogate endpoints, and longer-term follow-up is needed to confirm effects on kidney failure and safety outcomes.