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| Primary information |
|---|
| ID | 13936 |
| Therapeutic ID | Th1449 |
| Protein Name | Benralizumab |
| Sequence | >Th1449_Benralizumab
EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYVIHWVRQRPGQGLAWMGYINPYNDGTKYNERFKGKVTITSDRSTSTVYMELSSLRSEDTAVYLCGREGIRYYGLLGDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 146054 |
| Chemical Formula | C6492H10060N1724O2028S42 |
| Isoelectric Point | 6.6 - 7.2 |
| Hydrophobicity | NA |
| Melting point | 69 °C (midpoint transition), 80 °C (whole IgG1) |
| Half-life | The half-life of Benralizumab is estimated to be 15-18 days.[A31293] |
| Description | Benralizumab is a humanized recombinant monoclonal antibody of the isotype IgG1k immunoglobulin that specifically binds to the alpha chain of the interleukin 5 receptor (IL-5R) expressed on eosinophils and basophils.[A31294] It inhibits the binding of IL-5 as well as the hetero-oligomerization of the alpha and beta subunits of the IL-5R, thus blocking, signal transduction. Besides, it is an afucosylated IgG which gives it high affinity for the FcRIIIa receptor in natural killer cells, macrophages and neutrophils.[A31293] Benralizumab, FDA approved on November 14, 2017, was developed by MedImmune, the AstraZeneca's global biologic research and development arm.[L1019] |
| Indication/Disease | Benralizumab is indicated as a maintenance treatment of patients 12 years or older with severe asthma and an eosinophilic phenotype.[L1020] The pathology of severe asthma with eosinophilic phenotype is also denotated as TH2-high phenotype. The patients with this phenotype are characterized by the expression of IL-5 and IL-13, airway hyperresponsiveness, responsiveness to inhaled corticosteroids, high serum IgE and eosinophilia in blood and airway. In the TH2-high phenotype, IL-5 presents a central role as it is responsible for eosinophil differentiation, survival, activation and migration to the lungs.[A31295] |
| Pharmacodynamics | Eosinophils are the key target of inflammatory respiratory diseases and they undergo apoptosis in absence of IL-5. Therefore, benralizumab action on the IL-5 receptor in basophils and eosinophils produces the apoptosis and its significant reduction in the blood.[A31294] On the other hand, Benralizumab binding to natural killer cells FcRIIIa receptor produces a direct antibody-dependent cell-mediated cytotoxicity. All these effects produce a reduction in eosinophil count in airway mucosa, submucosa, sputum, blood and bone marrow.[A31296] |
| Mechanism of Action | Interleukin-5 (IL-5) induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils and some mast cells. Benralizumab, unlike IL-5 low-affinity binding, binds with high affinity to the domain I of the a-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent cell lines. On the other hand, Benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcRIIIa on natural killer cells, macrophages and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity.[A31293, A31295] |
| Toxicity | There are not reports of long-term studies regarding tumorgenesis or carcinogenesis. Fertility studies performed in aminal trials showed no adverse histopathological findings.[FDA label] |
| Metabolism | As any monoclonal IgG antibody, Beralizumab is degraded by proteases widely spread in the body. [FDA label] |
| Absorption | Subcutaneous administration of Benralizumab presented a dose-proportional pharmacokinetic profile. The administration of 20-200 mg presented an absorption half-life of 3.6 days with a bioavailability of 58%.[FDA label] It is also reported for Benralizumab a Cmax of 82 mcg/ml and AUC of 775 mcg day/ml.[A31293] |
| Pharmacokinetic reports of Benralizumab showed a volume of distribution in a range of 52-93ml/kg. For a 70kg individual, the central volume of distribution of Benralizumab is 3.2 L while the peripheral volume of distribution is reported to be 2.5 L.[A31297] |
| Clearance | For a subject weighting 70kg, the typical systemic clearance is 0.29L/day.[FDA label] |
| Categories | Antibodies, Monoclonal, Humanized |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-5 receptor subunit alpha,Low affinity immunoglobulin gamma Fc region receptor III-A |
| 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 |