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| Primary information |
|---|
| ID | 14485 |
| Therapeutic ID | Th1507 |
| Protein Name | Inebilizumab |
| Sequence | >Th1507_Inebilizumab
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSWMNWVRQAPGKGLEWVGRIYPGDGDTNYNVKFKGRFTISRDDSKNSLYLQMNSLKTEDTAVYYCARSGFITTVRDFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 149000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Inebilizumab exhibits biphasic pharmacokinetics with a mean terminal half-life of 18 days.[L14315] The terminal half-life reported in phase I studies varied by dose but was typically close to 18 days, with a range of 6.8 to 18.7 days.[A214298, A214301] |
| Description | Inappropriate growth of or self-directed antibody production by B-cells is the etiological underpinning of a variety of conditions, including the multiple sclerosis-like neurological condition neuromyelitis optica spectrum disorder (NMOSD).[A214283, A214286] Inebilizumab is a humanized afucosylated monoclonal IgG1 antibody directed against the broadly expressed B-cell surface antigen CD19. Inebilizumab is cytolytic, resulting in B-cell depletion and offering therapeutic benefit to patients suffering from NMOSD. Compared to the anti-CD20 antibody [rituximab], which is also used to treat NMOSD, inebilizumab has broader specificity.[A214280, A214289, A214292, A214295, A214298, A214301] Inebilizumab was granted FDA approval on June 11, 2020, for the treatment of anti-aquaporin 4 positive NMOSD patients.[L14315] Given its mechanism of action and good safety profile, it may prove useful in the treatment of other conditions linked to autoimmune antibody production or B-cell malignancies.[A214280, A214295] |
| Indication/Disease | Inebilizumab is indicated for the treatment of aquaporin-4 (AQP4) immunoglobulin-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD) in adult patients.[L14315] |
| Pharmacodynamics | Inebilizumab is a CD19-directed monoclonal antibody that results in immunosuppression through B-cell depletion with sufficient efficacy to allow a six-month dosing schedule.[A214280, A214289, A214292, L14315] Due to this mechanism of action, patients undergoing inebilizumab treatment may be at higher risk of infections and should be monitored for active infections and immunoglobulin levels while undergoing treatment; vaccination is not recommended during inebilizumab treatment. Also, there is a risk of severe infusion reactions. Animal data suggests the possibility of fetal harm with inebilizumab and therefore, effective contraception during and for six months following inebilizumab treatment is recommended.[L14315] |
| Mechanism of Action | Neuromyelitis optica spectrum disorder (NMOSD), formerly referred to as Devic's disease, is an antibody-mediated autoimmune condition resulting in astroglial cell death, demyelination, and central nervous system (CNS) inflammation.[A214283, A214286] The presence of anti-aquaporin 4 immunoglobulin (AQP4-IgG) is the most frequent biomarker, although AQP4-IgG negative, anti-myelin oligodendrocyte glycoprotein (anti-MOG) positive, variants with similar presentation also exist.[A214283, A214286] The theoretical origin of symptoms is through AQP4-IgG-mediated astrocyte cytotoxicity and subsequent infiltration of neutrophils, eosinophils, and macrophages, leading to inflammatory-mediated oligodendrocyte damage and myelin sheath loss.[A214286] In general, this manifests as optic neuritis and transverse myelitis with occasional involvement of the diencephalic, brainstem, and cerebral hemisphere.[A214295] CD19 is a B-cell surface antigen expressed on most B-cells,[A214280] including the expanded population of CD27high CD38high CD180- CD19+ plasmablasts that are the origin of astrocytic AQP4-IgG in most NMOSD patients.[A214283, A214286] Inebilizumab binds to CD19 and, through one of several potential mechanisms, results in cell death.[A214280, A214289, A214292, L14315] Destruction of the specific AQP4-IgG-producing plasmablasts results in lower amounts of AQP4-IgG in the CNS and therefore slows neuronal damage and improves patient outcomes.[A214295] |
| Toxicity | Toxicity information regarding inebilizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as severe infusion reactions, infections, and arthralgia. Symptomatic and supportive measures are recommended. |
| Metabolism | Inebilizumab is a monoclonal antibody and is hence likely degraded through proteolysis.[L14315] |
| Absorption | Inebilizumab is given intravenously and hence is immediately exposed to the systemic circulation. The mean reported Cmax following second dose 300 mg administration was 108 µg/mL, and the cumulative AUC following 26 weeks of treatment with two IV administrations was 2980 µg |
| Inebilizumab has an estimated central volume of distribution of 2.95L and a peripheral volume of distribution of 2.57L.[L14315] The steady-state volume of distribution in patients administered with a range of doses between 0.1 and 10.0 mg/kg ranged from 53.7 to 71.7 mL/kg.[A214301] |
| Clearance | Inebilizumab has an estimated systemic clearance of 0.19 L/day.[L14315] In phase I studies, the reported clearance varied between 139-180 mL/day in one study,[A214298] and 3.5-6.2 mL/kg/day in another,[A214301] depending on the dose. |
| Categories | Globulins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | B-lymphocyte antigen CD19 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |