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Abstract: TH-PO991

Interim Analysis (IA) of a Global Phase 2 Randomized Controlled Trial of Sibeprenlimab (VIS649), an APRIL-Neutralizing Monoclonal Antibody, in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States
  • Suzuki, Yusuke, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Chacko, Bobby, John Hunter Hospital, New Lambton Heights, New South Wales, Australia
  • Wong, Muh Geot, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  • Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
  • Oh, Kook-Hwan, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Sahay, Manisha, Osmania Medical College, Hyderabad, Telangana, India
  • Mathur, Mohit, Visterra Inc., Boston, Massachusetts, United States
  • Wang, Xiaofeng, Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, Maryland, United States
  • Yarbrough, Jill, Visterra Inc., Boston, Massachusetts, United States
  • Pereira, Brian J.G., Visterra Inc., Boston, Maryland, United States
Background

Pathogenesis of primary Immunoglobulin A Nephropathy (IgAN) is driven by A Proliferation-Inducing Ligand (APRIL). Sibeprenlimab is a humanized IgG2 monoclonal antibody that prevents APRIL signaling.

Methods

VIS649-201 (NCT04287985) is a global multicenter, randomized controlled study evaluating monthly intravenous (IV) Sibeprenlimab (2, 4, or 8 mg/kg) versus placebo in adults with IgAN on optimized supportive treatment, who have eGFR ≥ 30 ml/min/1.73m2 and proteinuria ≥ 1.0 g/d or urine protein creatinine ratio (uPCR) ≥ 0.75 g/g. A protocol specified group unblinded IA was conducted when 72 participants completed month-9 of a 12-month study course.

Results

Among pooled Sibeprenlimab recipients there was a 43% placebo-adjusted reduction from baseline in 24-hour uPCR values at month 9 (Figure 1a) with reduction in serum APRIL, total IgA & galactose-deficient IgA1. Among subjects with ≥ 9 months on study, the estimated annualized eGFR slope was stable (+1.2 mL/min/1.73m2/year) in pooled Sibeprenlimab recipients versus declining (-6.5 mL/min/1.73m2 /year) in the placebo group, with a slope difference of +7.7 mL/min/1.73m2/year (95% CI 1.32 to 14.01). The mean of eGFR change from baseline over time is shown in Figure 1b. No serious adverse events were considered study-drug related & most adverse events were mild or moderate in severity.

Conclusion

This Phase 2 IA of a precision therapeutic for IgAN, Sibeprenlimab, demonstrated acceptable safety & tolerability with robust uPCR reduction associated with eGFR stability, when compared to the placebo arm at 9 months of study follow up.

Funding

  • Commercial Support