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Kidney Week

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
ParameterSibeprenlimab
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.