Teprotumumab

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.[1]

Teprotumumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIGF-1R
Clinical data
Trade namesTepezza
Other namesTeprotumumab-trbw, RG-1507
License data
Routes of
administration		Intravenous
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
ECHA InfoCard100.081.384
Chemical and physical data
FormulaC6476H10012N1748O2000S40
Molar mass145639.97 g·mol−1
 NY (what is this?)  (verify)

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.[1] 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.[1]

It is a human monoclonal antibody developed by Genmab and Roche. It binds to IGF-1R.

Teprotumumab was approved for use in the United States in January 2020.[1][2][3][4] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[5]

Medical use

In a multicenter randomized trial in patients with active Graves' ophthalmopathy teprotumumab was more effective than placebo.[6] 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 patients treated with teprotumumab compared with placebo had a meaningful improvement in proptosis, or bulging of the eye: 82.9 percent of teprotumumab patients compared to 9.5 percent of placebo patients 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.[7] On 10 July 2019, Horizon submitted a Biologics License Application (BLA) to the FDA for teprotumumab for the treatment of active thyroid eye disease (TED). Horizon requested priority review for the application - if so granted (FDA has a 60-day review period to decide) it would result in a max. 6 month review process.[8]

History

Teprotumumab-trbw was approved for use in the United States in January 2020, for the treatment of adults with thyroid eye disease.[1][2]

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.[9] 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 hereon Horizon) acquired RVDC in 2017, and will continue clinical trials.[10] It is in Phase III trials for Graves' ophthalmopathy (also known as thyroid eye disease (TED)) and Phase I for diabetic macular edema.[11] It was granted Breakthrough Therapy, Orphan Drug Status and Fast Track designations by the FDA for Graves' ophthalmopathy.[10]

Teprotumumab-trbw was approved based on the results of two clinical trials (Trial 1/ NCT01868997 and Trial 2/ NCT03298867) of 170 subjects with active thyroid eye disease who were randomized to either receive teprotumumab-trbw or a placebo.[1][3] Of the subjects who were administered Tepezza, 71% in Study 1 and 83% in Study 2 demonstrated a greater than two millimeter reduction in proptosis (eye protrusion) as compared to 20% and 10% of subjects who received placebo, respectively.[1] The trials were conducted at 28 sites in Europe and United States.[3]

The U.S. Food and Drug Administration (FDA) granted the application for teprotumumab-trbw fast track designation, breakthrough therapy designation, priority review designation, and orphan drug designation.[1] The FDA granted the approval of Tepezza to Horizon Therapeutics Ireland DAC.[1]

References
  1. "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.
  2. "Teprotumumab-trbw: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 28 January 2020.
  3. "Drug Trial Snapshot: Tepezza". U.S. Food and Drug Administration (FDA). 29 January 2020. Retrieved 29 January 2020. This article incorporates text from this source, which is in the public domain.
  4. "Drug Approval Package: Tepezza". U.S. Food and Drug Administration (FDA). 2 March 2020. Retrieved 17 January 2021.
  5. "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Retrieved 17 January 2021. This article incorporates text from this source, which is in the public domain.
  6. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. (May 2017). "Teprotumumab for Thyroid-Associated Ophthalmopathy". The New England Journal of Medicine. 376 (18): 1748–1761. doi:10.1056/NEJMoa1614949. PMC 5718164. PMID 28467880.
  7. "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". Horizon Pharma plc. Retrieved 22 March 2019.
  8. "Horizon Therapeutics plc Submits Teprotumumab Biologics License Application (BLA) for the Treatment of Active Thyroid Eye Disease (TED)". Horizon Therapeutics plc. Retrieved 27 August 2019.
  9. Clinical trial number NCT01868997 for "Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease" at ClinicalTrials.gov
  10. "Teprotumumab". Genmab A/S.
  11. "Teprotumumab - Horizon Therapeutics plc". Adis International Ltd. Springer Nature Switzerland AG.
  • "Teprotumumab". Drug Information Portal. U.S. National Library of Medicine.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.