Repositioning Candidate Details
| Candidate ID: | R1453 |
| Source ID: | DB12530 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Inebilizumab |
| Synonyms: | Inebilizumab; inebilizumab-cdon |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank 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). 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 , which is also used to treat NMOSD, inebilizumab has broader specificity. Inebilizumab was granted FDA approval on June 11, 2020, for the treatment of anti-aquaporin 4 positive NMOSD patients. 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. |
| CAS Number: | 1299440-37-1 |
| Molecular Weight: | |
| DrugBank Indication: | Inebilizumab is indicated for the treatment of aquaporin-4 (AQP4) immunoglobulin-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD) in adult patients. |
| DrugBank Pharmacology: | 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. 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. |
| DrugBank MoA: | 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. 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. 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. In general, this manifests as optic neuritis and transverse myelitis with occasional involvement of the diencephalic, brainstem, and cerebral hemisphere. CD19 is a B-cell surface antigen expressed on most B-cells, including the expanded population of CD27<sup>high</sup> CD38<sup>high</sup> CD180<sup>-</sup> CD19<sup>+</sup> plasmablasts that are the origin of astrocytic AQP4-IgG in most NMOSD patients. Inebilizumab binds to CD19 and, through one of several potential mechanisms, results in cell death. 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. |
| Targets: | B-lymphocyte antigen CD19 binder |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|