Identification
- Summary
Teprotumumab is a fully human monoclonal antibody directed against insulin-like growth factor-1 receptor for the treatment of thyroid eye disease.
- Brand Names
- Tepezza
- Generic Name
- Teprotumumab
- DrugBank Accession Number
- DB06343
- Background
Teprotumumab is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor.8 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 20163 and was approved by the FDA in January 2020 for the treatment of TED.7 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.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 148000.0 Da (approximate)
- Sequences
- Not Available
- Synonyms
- Immunoglobulin G1, anti-(human insulin-like growth factor I receptor) (human monoclonal heavy chain), disulfide with human monoclonal light chain, dimer
- Teprotumumab
- teprotumumab-trbw
- External IDs
- R-1507
- R1507
- RG-1507
- RG1507
- RO-4858696
- RO-4858696-000
- RO-4858696000
- RO4858696
- RO4858696-000
- RV-001
- RV001
Pharmacology
- Indication
Teprotumumab is indicated for the treatment of thyroid eye disease.9
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.9,5 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.9
- Mechanism of action
Graves’ Disease is an autoimmune syndrome involving the thyroid, orbital connective tissues, and some regions of the skin.5 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.1 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.5 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.5
Teprotumumab is a fully human IgG1 monoclonal antibody directed against IGF-1R. It binds to and induces internalization and degradation of these receptors,1 thus preventing their downstream effects and alleviating symptoms of thyroid eye disease.9
Target Actions Organism UInsulin-like growth factor 1 receptor binderantibodyHumans - 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.9
- Volume of distribution
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.9
- Protein binding
Data regarding teprotumumab serum protein binding is unavailable at this time.
- 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.9
- Route of elimination
Data regarding specific route(s) of elimination are unavailable at this time.
- Half-life
The half-life of teprotumumab is 20 ± 5 days.9
- Clearance
The estimated mean clearance of teprotumumab is 0.27 L/day.9 The inter-compartment clearance is 0.74 L/day.9
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Toxicity information, including information regarding overdosage, is currently unavailable.9 Symptoms of teprotumumab overdose are likely to be consistent with its adverse effect profile.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Teprotumumab. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Teprotumumab. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Teprotumumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Teprotumumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Teprotumumab. Albiglutide The therapeutic efficacy of Albiglutide can be decreased when used in combination with Teprotumumab. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Teprotumumab. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Teprotumumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Teprotumumab. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Teprotumumab. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tepezza Injection, powder, lyophilized, for solution 500 mg/1 Intravenous Horizon Therapeutics USA, Inc. 2020-01-21 Not applicable US 
Categories
- ATC Codes
- L04AA53 — Teprotumumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antineoplastic and Immunomodulating Agents
- Globulins
- Hyperglycemia-Associated Agents
- Immunoproteins
- Immunosuppressive Agents
- Insulin-like Growth Factor-1 Receptor Inhibitor
- Insulin-like Growth Factor-1 Receptor Inhibitors
- Ototoxic agents
- Proteins
- Selective Immunosuppressants
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- Y64GQ0KC0A
- CAS number
- 1036734-93-6
References
- General References
- Wang Y, Patel A, Douglas RS: Thyroid Eye Disease: How A Novel Therapy May Change The Treatment Paradigm. Ther Clin Risk Manag. 2019 Nov 11;15:1305-1318. doi: 10.2147/TCRM.S193018. eCollection 2019. [Article]
- Hodgson NM, Rajaii F: Current Understanding of the Progression and Management of Thyroid Associated Orbitopathy: A Systematic Review. Ophthalmol Ther. 2019 Dec 10. pii: 10.1007/s40123-019-00226-9. doi: 10.1007/s40123-019-00226-9. [Article]
- Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS: Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949. [Article]
- Douglas RS: Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis. Eye (Lond). 2019 Feb;33(2):183-190. doi: 10.1038/s41433-018-0321-y. Epub 2018 Dec 21. [Article]
- Smith TJ: The insulin-like growth factor-I receptor and its role in thyroid-associated ophthalmopathy. Eye (Lond). 2019 Feb;33(2):200-205. doi: 10.1038/s41433-018-0265-2. Epub 2018 Nov 1. [Article]
- Mohyi M, Smith TJ: IGF1 receptor and thyroid-associated ophthalmopathy. J Mol Endocrinol. 2018 Jul;61(1):T29-T43. doi: 10.1530/JME-17-0276. Epub 2017 Dec 22. [Article]
- FDA News Release: Teprotumumab approval [Link]
- FDA Approved Drug Products: Tepezza (teprotumumab-trbw) for intravenous injection [Link]
- FDA Approved Drug Products: Tepezza (teprotumumab-trbw) for intravenous injection (December 2022) [Link]
- External Links
- 2274803
- Wikipedia
- Teprotumumab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Chronic (Inactive) Thyroid Eye Disease / Thyroid Eye Disease 1 4 Recruiting Treatment Thyroid Eye Disease 1 3 Completed Treatment Orbitopathy, Graves / Thyroid Eye Disease 1 3 Completed Treatment Thyroid Eye Disease 1 2 Completed Treatment Thyroid Associated Ophthalmopathy 1 2 Terminated Treatment Breast Cancer 1 2 Terminated Treatment Non-Small Cell Lung Cancer (NSCLC) 1 2 Terminated Treatment Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) 1 2 Terminated Treatment Sarcomas 1 1 Completed Basic Science Breast Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 500 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- BinderAntibody
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involv...
- Gene Name
- IGF1R
- Uniprot ID
- P08069
- Uniprot Name
- Insulin-like growth factor 1 receptor
- Molecular Weight
- 154791.73 Da
References
- FDA Approved Drug Products: Tepezza (teprotumumab-trbw) for intravenous injection [Link]
Drug created at March 19, 2008 16:25 / Updated at December 23, 2022 00:49