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| Primary information |
|---|
| ID | 10624 |
| Therapeutic ID | Th1126 |
| Protein Name | Belatacept |
| Sequence | >Th1126_Belatacept
MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 92300 |
| Chemical Formula | C3508H5440N922O1096S32 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Mean terminal elimination half-life: 10 mg/kg, kidney transplant recipients= 9.8 days; 5 mg/kg, kidney transplant recipient = 8.2 days |
| Description | Belatacept is a recombinant (CHO cells derived) soluble fusion protein, which links the extracellular domain of human cytotoxic CTLA-4 to the modified Fc portion of human IgG1, thereby selectively blocking the process of T-cell activation. It is a glycosylated fusion protein, which is a homodimer of two homologous polypeptide chains of 357 amino acids each. The drug acts as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. It differs from abatacept (Orencia) by only 2 amino acids. It is approved for the treatment of rheumatoid arthritis. It was developed by Bristol-Myers-Squibb. FDA approved on June 15, 2011. |
| Indication/Disease | For prophylaxis of organ rejection. It is also used concomitantly with basiliximumab for induction therapy, mycophenolate, and corticosteriods in kidney transplant recepients that are seropositive for the Epstein-Barr virus. |
| Pharmacodynamics | Belatacept binds to CD86 with a 4-fold higher affinity than abatacept. It also binds to CD80 with a 2-fold higher affinity than abatacept. It was observed in non-human primates that belatacept prolongs graft survival due to a decrease in antibody production against the donor organ. Furthermore, belatacept also inhibits the primary humoral immune response which is indicated by the decrease in post-transplant levels of IgG, IgM, and IgA. The magnitude of this effect is more significant in belatacept than it is in cyclosporine. |
| Mechanism of Action | Belatacept is a fusion protein in which the Fc portion of human IgG1 is attached onto the extracellular portion of human CTLA-4 (CD152). Belatacept specifically binds to CD80 and CD86 receptors that are found on the antigen-presenting cell (B cells, macrophages, dendritic cells) to block selective T-cell lymphocyte costimulation. CD80 and CD86 would normally act as the ligands to the CD28 receptor T-cells in which this interaction triggers the activation of T lymphocytes. However in the presence of belatacept, because the extracellular CTLA-4 component binds to CD28 with higher affinity than CD80 or CD86, T lymphyocyte anergy, a state of antigen specific tolerance, occurs instead. The T cell is also no longer able to respond to their antigen. |
| Toxicity | NA |
| Metabolism | The cytochrome P450 enzyme system or uridine diphosphate-glucuronosyltransferases are not expected to be involved with the metabolism of belatacept. Because the drug is a protein, belatacept is degraded into smaller peptides and amino acids by proteolytic enzymes. |
| Absorption | Following multiple intravenous doses of an initial 10 mg/kg dose and followed by a maintenance dose of 5 mg/kg in kidney transplant recipients, these are the following pharmacokinetic parameters: Cmax, 10 mg/kg = 247 µg/mL; Cmax, 5 mg/kg = 139 µg/mL; AUC, 10 mg/kg = 22,252 µg · h/mL; AUC, 5 mg/kg = 14,090 µg · h/mL; Belatacept had linear and dose-dependent pharmacokinetic profile. |
| Vd, steady state, transplant patients, 10 mg/kg = 0.11 L/kg; Vd, steady state, transplant patients, 5 mg/kg = 0.12 L/kg |
| Clearance | Increased body weight may increase the clearance rate of belatacept. Mean systemic clearance: 10 mg/kg, kidney transplant recipients= 0.49 mL/h/kg; 5 mg/kg, kidney transplant recipient = 0.51 mL/h/kg. |
| Categories | Antirheumatic Agents and Immunosuppressive Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | T-lymphocyte activation antigen CD86,T-lymphocyte activation antigen CD80 |
| Brand Name | Nulojix |
| Company | Bristol-Myers Squibb |
| Brand Description | Bristol-Myers Squibb |
| Prescribed For | NULOJIX (belatacept) is indicated for prophylaxis of organ rejection in adult patients receiving a kidney transplant. NULOJIX is to be used in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids. |
| Chemical Name | NA |
| Formulation | Prior to use, the lyophile is reconstituted with a suitable fluid to obtain a clear to slightly opalescent, colorless to pale yellow solution, with a pH in the range of 7.2 to 7.8. Suitable fluids for constitution of the lyophile include SWFI, 0.9% NS, or D5W. Each 250 mg single-use vial of NULOJIX also contains: monobasic sodium phosphate (34.5 mg), sodium chloride (5.8 mg), and sucrose (500 mg). |
| Physical Appearance | NULOJIX is supplied as a sterile, white or off-white lyophilized powder for intravenous administration. |
| Route of Administration | Intravenous Injection |
| Recommended Dosage | NA |
| Contraindication | Epstein-Barr virus (EBV) seronegative or with unknown EBV serostatus |
| Side Effects | PTLD, predominantly CNS PTLD, and other malignancies, EBV Seropositive Subpopulation, Progressive Multifocal Leukoencephalopathy, Bacterial, Mycobacterial, Viral, and Fungal Infections, Proteinuria, Immunogenicity, New-Onset Diabetes After Transplantation, Hypertension, Dyslipidemia |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |