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| Primary information |
|---|
| ID | 12753 |
| Therapeutic ID | Th1351 |
| Protein Name | Teprotumumab |
| Sequence | >Th1351_Teprotumumab
QVELVESGGGVVQPGRSQRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAIIWFDGSSTYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCARELGRRYFDLWGRGTLVSVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 148000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of teprotumumab is 20 ± 5 days.[L11359] |
| Description | Teprotumumab is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor.[L11359] Following a clinical trial in which its efficacy in the treatment of thyroid eye disease (TED) was assessed, it received "breakthrough therapy" designation from the FDA in 2016[A190129] and was approved by the FDA in January 2020 for the treatment of TED.[L11350] Thyroid eye disease is a potentially debilitating complication of Graves' Disease involving inflammation and tissue remodeling behind the eye, and previous treatment options typically involved multiple invasive surgeries - teprotumumab is the first drug ever approved for the treatment of TED and therefore represents a significant step forward in the treatment this disease.[L11350] |
| Indication/Disease | Teprotumumab is indicated for the treatment of thyroid eye disease.[L11359] |
| Pharmacodynamics | Teprotumumab inhibits the downstream effects of IGF-1R signaling, namely tissue inflammation and remodeling, which are responsible for the various symptoms of thyroid eye disease.[L11359,A190138] Teprotumumab may cause disease flares in patients with pre-existing inflammatory bowel disease (IBD) - patients experiencing an exacerbation should discontinue therapy with teprotumumab. Significant hyperglycemia has been observed in patients receiving treatment with teprotumumab which may require antihyperglycemic medications. Based on its mechanism of action, it is likely that teprotumumab will cause fetal harm in pregnant woman - for this reason, females of child-bearing age should use effective contraception prior to initiation, during therapy, and for 6 months following the last dose of teprotumumab.[L11359] |
| Mechanism of Action | Graves’ Disease is an autoimmune syndrome involving the thyroid, orbital connective tissues, and some regions of the skin.[A190138] One manifestation of Graves’ Disease is thyroid-associated ophthalmopathy, or thyroid eye disease, which is characterized by orbital inflammation, tissue remodeling, and fibrosis. As the disease progresses, patients may develop proptosis, strabismus, corneal ulceration, and optic neuropathy.[A189937] It has been demonstrated that insulin-like growth factor-1 receptors (IGF-1R) are overexpressed by orbital fibroblasts in patients with thyroid eye disease, in addition to being overexpressed on T-cells and B-cells in these patients.[A190138] It was found that Graves’ Disease IgG molecules could mimic the principal ligand of IGF-1R, insulin-like growth factor-1 (IGF-1), and their binding of IGF-1R induces the expression of chemokines that play roles in tissue remodeling and inflammation. For these reasons, IGF-1R was sought after as a potential therapeutic target for the treatment of thyroid eye disease.[A190138] Teprotumumab is a fully human IgG1 monoclonal antibody directed against IGF-1R. It binds to and induces internalization and degradation of these receptors,[A189937] thus preventing their downstream effects and alleviating symptoms of thyroid eye disease.[L11359] |
| Toxicity | Toxicity information, including information regarding overdosage, is currently unavailable.[L11359] Symptoms of teprotumumab overdose are likely to be consistent with its adverse effect profile. |
| Metabolism | The metabolism of teprotumumab has not been fully characterized. As a protein, its metabolism is expected to involve proteolysis to smaller proteins and peptides.[L11359] |
| Absorption | In a population of 40 patients receiving standard dosing in two clinical trials of teprotumumab, utilizing a two-compartment pharmacokinetic model, the AUC and Cmax were estimated to be 138 ± 34 mg•hr/mL and 632 ± 139 mcg/mL, respectively.[L11359] |
| Following the standard dosing regimen, the mean central and peripheral volumes of distribution are approximately 3.26 ± 0.87 L and 4.32 ± 0.67 L, respectively.[L11359] |
| Clearance | The estimated mean clearance of teprotumumab is 0.27 L/day.[L11359] The inter-compartment clearance is 0.74 L/day.[L11359] |
| Categories | Insulin-like Growth Factor-1 Receptor Inhibitors |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Insulin-like growth factor 1 receptor |
| 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 |