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| Primary information |
|---|
| ID | 10736 |
| Therapeutic ID | Th1170 |
| Protein Name | Blinatumomab |
| Sequence | >Th1170_Blinatumomab
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSGGGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGLEWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPAIMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPYRFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKHHHHHH
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| Molecular Weight | 54100 |
| Chemical Formula | C2367H3577N649O772S19 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 2.11 hours, standard deviation 1.42. |
| Description | Blinatumomab is a BiTE-class (bi-specific T-cell engagers) constructed monoclonal antibody indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Blinatumomab is manufactured by Amgen Inc. and marketed under the brand Blincyto™. A full treatment regimen consisting of two cycles of four weeks each, is priced at $178 000 USD. Blinatumomab was approved in December 2014 under the FDA’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. |
| Indication/Disease | Indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). |
| Pharmacodynamics | NA |
| Mechanism of Action | Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenous T cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells. Blinatumomab mediates the formation of a synapse between the T cell and the tumor cell, upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells. |
| Toxicity | - Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended. - Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended. - In patients receiving blinatumomab in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections were observed in approximately 25% of patients, some of which were life-threatening or fatal. - Tumor lysis syndrome (TLS), which may be life-threatening or fatal, has been observed in patients. - Neutropenia and febrile neutropenia, including life-threatening cases, have been observed in patients. - Treatment with blinatumomab was associated with transient elevations in liver enzymes. - Cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving blinatumomab, especially in patients with prior treatment with cranial irradiation and antileukemic chemotherapy (including systemic high-dose methotrexate or intrathecal cytarabine). |
| Metabolism | The metabolic pathway of blinatumomab has not been characterized. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways. |
| Absorption | NA |
| 4.52 L, standard deviation 2.89. |
| Clearance | 2.92 L/hour, standard deviation 2.83. |
| Categories | Amides,Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antineoplastic Agents,Antineoplastic and Immunomodulating Agents,Bispecific CD19-directed CD3-directed T Cell Engager,Blood Proteins,Cancer immunotherapy,CD19-directed Antibody Interactions,CD3 Receptor Agonists,CD3-directed Antibody Interactions,Globulins,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Monoterpenes,Myelosuppressive Agents,Narrow Therapeutic Index Drugs,Norbornanes,Proteins,Serum Globulins,Sulfones,Sulfur Compounds,Terpenes |
| Patents Number | US20120328618 |
| Date of Issue | 27-10-2009 |
| Date of Expiry | 27-10-2029 |
| Drug Interaction | The risk or severity of adverse effects can be increased when Blinatumomab is combined with Clozapine; The risk or severity of adverse effects can be increased when Denosumab is combined with Blinatumomab; The risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide; The risk or severity of adverse effects can be increased when Metamizole is combined with Blinatumomab; The risk or severity of adverse effects can be increased when Blinatumomab is combined with Natalizumab; The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Blinatumomab; Roflumilast may increase the immunosuppressive activities of Blinatumomab; The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Blinatumomab; The risk or severity of adverse effects can be increased when Tacrolimus is combined with Blinatumomab; Blinatumomab may increase the immunosuppressive activities of Tofacitinib. |
| Target | B-lymphocyte antigen CD19,T-cell surface glycoprotein CD3 delta chain |
| Brand Name | Blincyto |
| Company | AMGEN |
| Brand Description | AMGEN |
| Prescribed For | BLINCYTO is indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). |
| Chemical Name | NA |
| Formulation | 12.5 mcg/mL |
| Physical Appearance | lyophilized powder for intravenous administration |
| Route of Administration | Intravenous |
| Recommended Dosage | A single cycle of treatment of BLINCYTO consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval. For patients at least 45 kg in weight: In Cycle 1, administer BLINCYTO at 9 mcg/day on Days 1–7 and at 28 mcg/day on Days 8–28. For subsequent cycles, administer BLINCYTO at 28 mcg/day on Days 1–28. Allow for at least 2 weeks treatment-free between cycles of BLINCYTO. A treatment course consists of up to 2 cycles of BLINCYTO for induction followed by 3 additional cycles for consolidation treatment (up to a total of 5 cycles). |
| Contraindication | BLINCYTO is contraindicated in patients with known hypersensitivity to blinatumomab or to any component of the product formulation. |
| Side Effects | Cytokine Release Syndrome; Neurological Toxicities; Infections; Tumor Lysis Syndrome; Neutropenia and Febrile Neutropenia; Effects on Ability to Drive and Use Machines; Elevated Liver Enzymes; Leukoencephalopathy; Preparation and Administration Errors. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |