sibeprenlimab

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Ligands
sibeprenlimab

GtoPdb Ligand ID: 12102

Synonyms: sibeprenlimab-szsi | VIS-649 | VIS649 | Voyxact®

sibeprenlimab is an approved drug

Compound class: Antibody

Comment: Sibeprenlimab (VIS-649) is a fully humanized IgG2κ monoclonal antibody that targets the B-cell growth factor APRIL (TNFSF13) [2,5]. The antibody binds with high affinity to human trimeric APRIL, and potently blocks APRIL binding to its receptors TACI (transmembrane activator and CAML interactor) and BCMA (B-cell maturation antigen). APRIL mediates antibody class switching in mature B cells and promotes plasma-cell survival. APRIL acts to elevate production of IgA and pathogenic galactose-deficient IgA1, by mediating class switching in mature B cells and promoting plasma-cell survival. Galactose-deficient IgA1 is a key driver of the IgA nephropathy pathology. Hence targeting APRIL is considered as a mechanism to reduce IgA-mediated kidney damage.

References
1. Doggrell SA. (2024) Sibeprenlimab, which neutralizes A PRoliferation Inducing Ligand (APRIL), as a new approach to treating IgA nephropathy. Expert Opin Biol Ther, 24 (5): 335-338. [PMID:38641998]
2. Lemley KV, Glassock RJ. (2024) APRIL - Springtime for New IgA Nephropathy Therapy?. N Engl J Med, 390 (1): 80-81. [PMID:38169494]
3. Mathur M, Barratt J, Chacko B, Chan TM, Kooienga L, Oh KH, Sahay M, Suzuki Y, Wong MG, Yarbrough J et al.. (2024) A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. N Engl J Med, 390 (1): 20-31. [PMID:37916620]
4. Mathur M, Barratt J, Suzuki Y, Engler F, Pasetti MF, Yarbrough J, Sloan S, Oldach D. (2022) Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG₂ Monoclonal Antibody, in Healthy Volunteers. Kidney Int Rep, 7 (5): 993-1003. [PMID:35570983]
5. Myette JR, Kano T, Suzuki H, Sloan SE, Szretter KJ, Ramakrishnan B, Adari H, Deotale KD, Engler F, Shriver Z et al.. (2019) A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy. Kidney Int, 96 (1): 104-116. [PMID:31027890]
6. Perkovic V, Trimarchi H, Tesar V, Lafayette R, Wong MG, Barratt J, Suzuki Y, Liew A, Zhang H, Carroll K et al.. (2025) Sibeprenlimab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial. N Engl J Med, [Epub ahead of print]. [PMID:41211929]

References

1. Doggrell SA. (2024)
Sibeprenlimab, which neutralizes A PRoliferation Inducing Ligand (APRIL), as a new approach to treating IgA nephropathy.
Expert Opin Biol Ther, 24 (5): 335-338. [PMID:38641998]

2. Lemley KV, Glassock RJ. (2024)
APRIL - Springtime for New IgA Nephropathy Therapy?.
N Engl J Med, 390 (1): 80-81. [PMID:38169494]

3. Mathur M, Barratt J, Chacko B, Chan TM, Kooienga L, Oh KH, Sahay M, Suzuki Y, Wong MG, Yarbrough J et al.. (2024)
A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy.
N Engl J Med, 390 (1): 20-31. [PMID:37916620]

4. Mathur M, Barratt J, Suzuki Y, Engler F, Pasetti MF, Yarbrough J, Sloan S, Oldach D. (2022)
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG₂ Monoclonal Antibody, in Healthy Volunteers.
Kidney Int Rep, 7 (5): 993-1003. [PMID:35570983]

5. Myette JR, Kano T, Suzuki H, Sloan SE, Szretter KJ, Ramakrishnan B, Adari H, Deotale KD, Engler F, Shriver Z et al.. (2019)
A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy.
Kidney Int, 96 (1): 104-116. [PMID:31027890]

6. Perkovic V, Trimarchi H, Tesar V, Lafayette R, Wong MG, Barratt J, Suzuki Y, Liew A, Zhang H, Carroll K et al.. (2025)
Sibeprenlimab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial.
N Engl J Med, [Epub ahead of print]. [PMID:41211929]