Chemistry:Teprotumumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | IGF-1R |
| Clinical data | |
| Trade names | Tepezza |
| Other names | Teprotumumab-trbw, RG-1507 |
| License data |
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| Routes of administration | Intravenous |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C6476H10012N1748O2000S40 |
| Molar mass | 145639.97 g·mol−1 |
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Teprotumumab, sold under the brand name Tepezza, is a medication used to treat adults with thyroid eye disease, a rare condition where the muscles and fatty tissues behind the eye become inflamed, causing the eyes to bulge outwards.[2][3]
The most common side effects are muscle spasm, nausea, hair loss, diarrhea, fatigue, high blood sugar, hearing loss, dry skin, altered sense of taste, and headache.[3] Teprotumumab should not be used if pregnant, and women of child-bearing potential should have their pregnancy status verified prior to beginning treatment and should be counseled on pregnancy prevention during treatment and for six months following the last dose.[3]
It is a human monoclonal antibody developed by Genmab and Roche[4] for tumour treatment but was later researched by River Vision Development Corporation and Horizon Therapeutics to be used for ophthalmic uses.[5] It binds to IGF-1R.[1]
Teprotumumab was approved for use in the United States in January 2020.[3][6][7][8] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[9]
Medical use
In a multicenter, randomized trial in participants with active Graves' ophthalmopathy, teprotumumab was more effective than placebo.[10] In February 2019, Horizon announced results from a Phase III confirmatory trial evaluating teprotumumab for the treatment of active thyroid eye disease (TED). The study met its primary endpoint, showing more participants treated with teprotumumab compared with placebo had a meaningful improvement in proptosis, or bulging of the eye: 82.9% of teprotumumab participants compared to 9.5% of placebo participants achieved the primary endpoint of a 2 mm or more reduction in proptosis (p<0.001). Proptosis is the main cause of morbidity in TED. All secondary endpoints were also met and the safety profile was consistent with the Phase II study of teprotumumab in TED.[11] On 10 July 2019, Horizon submitted a biologics license application to the FDA for teprotumumab for the treatment of active thyroid eye disease. Horizon requested priority review for the application - if so granted (FDA has a 60-day review period to decide) it would result in a maximum 6-month review process.[12]
History
Teprotumumab-trbw was approved for use in the United States in January 2020, for the treatment of adults with thyroid eye disease (TED).[3][6]
Teprotumumab was first investigated for the treatment of solid and hematologic tumors, including breast cancer, Hodgkin's and non-Hodgkin's lymphoma, non-small cell lung cancer, and sarcoma.[13] Although results of phase I and early phase II trials showed promise, research for these indications were discontinued in 2009, by Roche. Phase II trials still in progress were allowed to complete, as the development was halted due to business prioritization rather than safety concerns.
Teprotumumab was subsequently licensed to River Vision Development Corporation in 2012, for research in the treatment of ophthalmic conditions. Horizon Pharma (now Horizon Therapeutics, from here on Horizon) acquired RVDC in 2017, and will continue clinical trials.[14] It is in phase III trials for Graves' ophthalmopathy (TED) and phase I for diabetic macular edema.[15] It was granted Breakthrough Therapy, Orphan Drug Status and Fast Track designations by the FDA for Graves' ophthalmopathy.[14]
Teprotumumab-trbw was approved based on the results of two clinical trials (Trial 1/ NCT01868997 and Trial 2/ NCT03298867) of 170 subjects with active TED who were randomized to either receive teprotumumab-trbw or a placebo.[3][7] Of the subjects who were administered Tepezza, 71% in study 1 and 83% in study 2 demonstrated a greater than 2 mm reduction in proptosis (eye protrusion) as compared to 20% and 10% of subjects who received placebo, respectively.[3] The trials were conducted at 28 sites in Europe and United States.[7]
The FDA granted the application for teprotumumab-trbw fast-track, breakthrough therapy, priority review, and orphan drug designations.[3] The FDA granted the approval of Tepezza to Horizon Therapeutics Ireland DAC.[3]
References
- ↑ 1.0 1.1 "Tepezza- teprotumumab injection, powder, lyophilized, for solution". 24 July 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e6c54a1-cefd-4a5b-a855-ab9f268b6cce.
- ↑ "A Novel Case of Hyperglycemic Hyperosmolar State After the Use of Teprotumumab in a Patient With Thyroid Eye Disease" (in English). AACE Clinical Case Reports 8 (4): 148–149. 1 July 2022. doi:10.1016/j.aace.2022.01.004. PMID 35959086.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "FDA approves first treatment for thyroid eye disease". U.S. Food and Drug Administration (FDA) (Press release). 21 January 2020. Retrieved 21 January 2020.
This article incorporates text from this source, which is in the public domain.
- ↑ "Teprotumumab (Tepezza): from the discovery and development of medicines to USFDA approval for active thyroid eye disease (TED) treatment". International Ophthalmology 41 (4): 1549–1561. April 2021. doi:10.1007/s10792-021-01706-3. PMID 33481154.
- ↑ "Horizon Pharma plc Announces Agreement to Acquire River Vision Development Corp. and Teprotumumab (RV001), a Biologic in Late-Stage Development for Rare Eye Disease" (Press release). Horizon Pharma. 8 May 2017. Retrieved 22 August 2022 – via GlobeNewswire.
- ↑ 6.0 6.1 "Teprotumumab-trbw: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=761143.
- ↑ 7.0 7.1 7.2 "Drug Trial Snapshot: Tepezza". 29 January 2020. http://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-tepezza. This article incorporates text from this source, which is in the public domain.
- ↑ "Drug Approval Package: Tepezza". 4 June 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/761143Orig1s000TOC.cfm.
- ↑ "New Drug Therapy Approvals 2020". 31 December 2020. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2020. This article incorporates text from this source, which is in the public domain.
- ↑ "Teprotumumab for Thyroid-Associated Ophthalmopathy". The New England Journal of Medicine 376 (18): 1748–1761. May 2017. doi:10.1056/NEJMoa1614949. PMID 28467880.
- ↑ "Horizon Pharma plc Announces Phase 3 Confirmatory Trial Evaluating Teprotumumab (OPTIC) for the Treatment of Active Thyroid Eye Disease (TED) Met Primary and All Secondary Endpoints". http://ir.horizon-pharma.com/news-releases/news-release-details/horizon-pharma-plc-announces-phase-3-confirmatory-trial.
- ↑ "Horizon Therapeutics plc Submits Teprotumumab Biologics License Application (BLA) for the Treatment of Active Thyroid Eye Disease (TED)" (in en). https://ir.horizontherapeutics.com/news-releases/news-release-details/horizon-therapeutics-plc-submits-teprotumumab-biologics-license.
- ↑ Clinical trial number NCT01868997 for "Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease" at ClinicalTrials.gov
- ↑ 14.0 14.1 "Teprotumumab". Genmab A/S. https://www.genmab.com/product-pipeline/products-in-development/teprotumumab.
- ↑ "Teprotumumab - Horizon Therapeutics plc". Adis International Ltd.. Springer Nature Switzerland AG. http://adisinsight.springer.com/drugs/800015801.
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