Abstract: FR-PO0813
Povetacicept for IgAN: Design of a Phase 3 Randomized, Placebo-Controlled Study
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Li, Jiahua, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
- Xuan, Fengjuan, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
- Egbuna, Ogo I., Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
Background
IgA nephropathy (IgAN), a leading cause of glomerulonephritis and end-stage kidney disease (ESKD), arises from genetic and environmental factors stimulating B-cells to produce Gd-IgA1, an autoantigen. This leads to autoantibody generation, immune complex deposition, and subsequent glomerular injury. BAFF and APRIL regulate B-cell maturation and immune responses, which is critical to IgAN disease pathology. By modulating the immune response, BAFF/APRIL inhibition can be a disease-modifying therapy compared to current therapies targeting secondary effects. Povetacicept is a dual BAFF/APRIL inhibitor with potential to reduce proteinuria and stabilize renal function. Interim RUBY-3 phase 1/2 data demonstrated a 66% mean reduction in 24-hr urine protein-to-creatinine ratio (UPCR), stable eGFR, and 63% clinical remission (UPCR <0.5g/g, negative hematuria, stable renal function) through 48wks (n=8) in participants with IgAN receiving subcutaneous povetacicept (80mg every 4wks).
Methods
RAINIER is an ongoing global phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of povetacicept in participants (n=480) aged ≥18yrs with biopsy-confirmed IgAN, persistent proteinuria (≥1.0g/day or 24-hr UPCR ≥0.75g/g), and an eGFR of ≥30ml/min/1.73m2. Participants are randomized 2:1 to receive subcutaneous povetacicept 80mg or placebo every 4wks for 104wks. Randomization will be stratified by mean UPCR, eGFR, and geographic region.
Results
The primary endpoint will evaluate the change from baseline in 24-hr UPCR at wk36 and the total eGFR slope through wk104. Secondary endpoints include change from baseline in eGFR at wk104, time to kidney disease progression (≥30% decline in eGFR, ESKD, or death from kidney failure through wk104), and change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue score at wk104. Safety will also be evaluated. An interim analysis will occur after 36wks of treatment, with the potential to file for Accelerated Approval in the US.
Conclusion
Povetacicept demonstrated significant efficacy in reducing proteinuria and stabilizing renal function in Phase 1/2. The RAINIER Phase 3 study will confirm the clinical benefits previously observed and support the potential of povetacicept as a treatment for IgAN.
Funding
- Commercial Support – Vertex Pharmaceuticals Incorporated