concizumab

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Ligands
concizumab

GtoPdb Ligand ID: 11182

Synonyms: Alhemo® | Anti-TFPI | mab2021 | NN7415

concizumab is an approved drug (Health Canada (2023))

Comment: Concizumab is a clinical stage anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody. It is a humanised IgG4 construct that was developed by Novo Nordisk as a novel therapeutic for genetic bleeding disorders [2]. Concizumab binds to the Kunitz-type protease inhibitor (KPI) 2 domain of TFPI and blocks its interaction with the active site of FXa [1]. TFPI is an endogenous anticoagulant protein whose pharmacological inhibition restores hemostasis [7].

References
1. Agersø H, Overgaard RV, Petersen MB, Hansen L, Hermit MB, Sørensen MH, Petersen LC, Hilden I. (2014) Pharmacokinetics of an anti-TFPI monoclonal antibody (concizumab) blocking the TFPI interaction with the active site of FXa in Cynomolgus monkeys after iv and sc administration. Eur J Pharm Sci, 56: 65-9. [PMID:24568891]
2. Franchini M, Marano G, Pati I, Veropalumbo E, Vaglio S, Pupella S, Masiello F, Cruciani M, Mengoli C, Liumbruno GM. (2020) Investigational drugs to treat hemophilia. Expert Opin Investig Drugs, 29 (3): 295-301. [PMID:32008381]
3. Hansen L, Petersen LC, Lauritzen B, Clausen JT, Grell SN, Agersø H, Sørensen BB, Hilden I, Almholt K. (2014) Target-mediated clearance and bio-distribution of a monoclonal antibody against the Kunitz-type protease inhibitor 2 domain of Tissue Factor Pathway Inhibitor. Thromb Res, 133 (3): 464-71. [PMID:24393663]
4. Hilden I, Lauritzen B, Sørensen BB, Clausen JT, Jespersgaard C, Krogh BO, Bowler AN, Breinholt J, Gruhler A, Svensson LA et al.. (2012) Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model. Blood, 119 (24): 5871-8. [PMID:22563084]
5. Keam SJ. (2023) Concizumab: First Approval. Drugs, 83 (11): 1053-1059. [PMID:37341887]
6. Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Chowdary P, Eichler H, Jiménez-Yuste V, Kavakli K, Matsushita T et al.. (2019) Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results. Blood, 134 (22): 1973-1982. [PMID:31444162]
7. Sidonio RF, Zimowski KL. (2019) TFPI blockade: removing coagulation's brakes. Blood, 134 (22): 1885-1887. [PMID:31778542]

References

1. Agersø H, Overgaard RV, Petersen MB, Hansen L, Hermit MB, Sørensen MH, Petersen LC, Hilden I. (2014)
Pharmacokinetics of an anti-TFPI monoclonal antibody (concizumab) blocking the TFPI interaction with the active site of FXa in Cynomolgus monkeys after iv and sc administration.
Eur J Pharm Sci, 56: 65-9. [PMID:24568891]

2. Franchini M, Marano G, Pati I, Veropalumbo E, Vaglio S, Pupella S, Masiello F, Cruciani M, Mengoli C, Liumbruno GM. (2020)
Investigational drugs to treat hemophilia.
Expert Opin Investig Drugs, 29 (3): 295-301. [PMID:32008381]

3. Hansen L, Petersen LC, Lauritzen B, Clausen JT, Grell SN, Agersø H, Sørensen BB, Hilden I, Almholt K. (2014)
Target-mediated clearance and bio-distribution of a monoclonal antibody against the Kunitz-type protease inhibitor 2 domain of Tissue Factor Pathway Inhibitor.
Thromb Res, 133 (3): 464-71. [PMID:24393663]

4. Hilden I, Lauritzen B, Sørensen BB, Clausen JT, Jespersgaard C, Krogh BO, Bowler AN, Breinholt J, Gruhler A, Svensson LA et al.. (2012)
Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model.
Blood, 119 (24): 5871-8. [PMID:22563084]

5. Keam SJ. (2023)
Concizumab: First Approval.
Drugs, 83 (11): 1053-1059. [PMID:37341887]

6. Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Chowdary P, Eichler H, Jiménez-Yuste V, Kavakli K, Matsushita T et al.. (2019)
Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results.
Blood, 134 (22): 1973-1982. [PMID:31444162]

7. Sidonio RF, Zimowski KL. (2019)
TFPI blockade: removing coagulation's brakes.
Blood, 134 (22): 1885-1887. [PMID:31778542]