Abstract: TH-PO1124
Sibeprenlimab in Patients with IgA Nephropathy: A Phase 2 Trial
Session Information
- Late-Breaking Posters
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Barratt, Jonathan, John Walls Renal Unit, Leicester General Hospital, Leicester, United Kingdom
- Mathur, Mohit, Visterra, Inc., Waltham, Massachusetts, United States
- Chacko, Bobby, Nephrology and Transplantation, John Hunter Hospital and University of Newcastle, Newcastle, New South Wales, Australia
- Chan, Tak Mao Daniel, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States
- Oh, Kook-Hwan, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
- Sahay, Manisha, Osmania General Hospital, Hyderabad, India
- Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Wong, Muh Geot, University of Sydney, Sydney, New South Wales, Australia
- Yarbrough, Jill, Visterra, Inc., Waltham, Massachusetts, United States
- Xia, Jing, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States
- Pereira, Brian J.G., Visterra, Inc., Waltham, Massachusetts, United States
Background
A Proliferation-Inducing Ligand (APRIL) is implicated in the pathogenesis of immunoglobulin A nephropathy (IgAN). Sibeprenlimab is a humanized IgG2 monoclonal antibody that blocks APRIL signaling.
Methods
VIS649-201 (NCT04287985) is a global, multicenter, randomized, double-blind, placebo-controlled study evaluating monthly intravenous (IV) sibeprenlimab 2, 4 or 8 mg/kg added to background optimized renin–angiotensin–aldosterone system blockade for 12 months in adults with IgAN. Patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, and proteinuria ≥1.0 g/d or urine protein creatinine ratio (uPCR) ≥0.75 g/g, were included.
Results
155 participants were randomized: 56.8% male; 74.2% Asian; median age 39 years. At Month 12, compared with placebo, sibeprenlimab groups demonstrated significant reductions in 24-hour uPCR (Figure, Table) and clinically relevant smaller changes in eGFR (sibeprenlimab, −2.7 to +0.2 mL/min/1.73 m2; placebo, −7.4 mL/min/1.73 m2; Table). The incidence of treatment-emergent adverse events (TEAEs) was 78.6% (sibeprenlimab pooled) and 71.1% (placebo), with comparable distribution of serious, severe, and drug-related TEAEs.
Conclusion
These results suggest that IV sibeprenlimab may provide an effective and well-tolerated treatment option to slow disease progression of IgAN, and support the ongoing Phase 3 VISIONARY trial of subcutaneous sibeprenlimab in patients with IgAN (NCT05248646).
Efficacy and Safety Data
| Parameter | Sibeprenlimab 2 mg/kg (n = 38) | Sibeprenlimab 4 mg/kg (n = 41) | Sibeprenlimab 8 mg/kg (n = 38) | Placebo (n = 38) |
| Median baseline urine protein excretion, g/day (range) | 1.47 (0.67–6.92) | 1.93 (0.33–8.60) | 1.90 (0.76–12.44) | 2.13 (0.76–8.48) |
| Geometric mean ratio reduction in 24-h uPCR from baseline at Month 12, % (standard error) | 47.2 (8.2) | 58.8 (6.1) | 62.0 (5.7) | 20.0 (12.6) |
| Geometric mean uPCR reduction at Month 12 relative to placebo, % (standard error) | 33.96 (13.7) P = 0.048 | 48.45 (10.4) P = 0.0013 | 52.52 (9.7) P = 0.0004 | – |
| Median baseline eGFR, mL/min/1.73 m2 (range) | 58.0 (35.0–154.0) | 64.0 (35.0–133.0) | 56.0 (34.0–109.0) | 68.5 (33.0–116.0) |
| Least squares mean eGFR change from baseline at Month 12, mL/min/1.73 m2 (standard error) | −2.7 (1.8) | +0.2 (1.7) | −1.5 (1.8) | −7.4 (1.8) |
| Least squares mean difference in eGFR at Month 12 relative to placebo, mL/min/1.73 m2 (standard error) | +4.6 (2.5) P = 0.063 | +7.6 (2.4) P = 0.002 | +5.8 (2.5) P = 0.020 | – |
| Any TEAE, n (%)* | 28 (73.7) | 33 (80.5) | 31 (81.6) | 27 (71.1) |
| Serious TEAE, n (%) | 2 (5.3) | 2 (4.9) | 1 (2.6) | 2 (5.3) |
*Lower incidence of infections in pooled sibeprenlimab group vs placebo.
Percentage Change in 24-Hour uPCR From Baseline Over Time
Funding
- Commercial Support – Visterra, Inc. (Waltham, MA), a member of the Otsuka family of companies.