Teplizumab

Source: Wikipedia, the free encyclopedia.
Teplizumab
Humanized (from mouse)
TargetCD3
Clinical data
Trade namesTzield
Other namesteplizumab-mzwv, PRV-031,[1] MGA031
License data
Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6462H9938N1738O2022S46
Molar mass145801.49 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Teplizumab, sold under the brand name Tzield, is a humanized anti-CD3 monoclonal antibody that is the first approved treatment indicated to delay the onset of stage 3 type 1 diabetes (T1D) in people with stage 2 T1D.[3][4][5]

The

Fc region of this antibody has been engineered to have Fc receptor non-binding (FNB) properties.[6] The mechanisms of action of teplizumab appear to involve weak agonistic activity on signaling via the T cell receptor-CD3 complex associated with the development of anergy, unresponsiveness, and/or apoptosis, particularly of unwanted activated Teff cells. In addition, regulatory cytokines are released and regulatory T cells are expanded that may lead to the reestablishment of immune tolerance [7][8]

Teplizumab was approved for medical use in the United States in November 2022.[9] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[10][11]

Medical uses

Teplizumab is

indicated to delay the onset of stage 3 type 1 diabetes (T1D) people aged eight years of age and older with stage 2 T1D.[2][3]

History

Teplizumab was developed at the University of Chicago in partnership with Ortho Pharmaceuticals, and was then further developed at MacroGenics, Inc.,[12][13] including a collaboration with Eli Lilly to conduct the first Phase 3 clinical trial in early-onset type 1 diabetes.[14] After the initial Phase 3 trial conducted by Macrogenics failed to meet the primary endpoint,[15] the drug was acquired by Provention Bio, which restarted development based on subset analysis of the original trials.[16][17]

Research

Teplizumab has been used in clinical trials with the aim of protecting the remaining β-cells in newly diagnosed type 1 diabetes patients.[18] Immunomodulatory agents such as anti-CD3-antibodies may restore normal glucose control if provided in very early stages of the disease, such as stage 2 T1DM, when there are still enough beta cells to maintain euglycemia.[19]

Teplizumab has been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis.[20]

A phase II study showed that teplizumab could delay the development of diabetes in family members of type 1 diabetics showing signs of progression towards diabetes by about two years after a single treatment, renewing interest in its use as a preventive rather than therapeutic treatment in high-risk patients.[21]

References

  1. ^ "Provention Bio Announces PRV-031 (Teplizumab) Granted PRIME Designation by the European Medicines Agency" (Press release). Provention Bio. 24 October 2019. Retrieved 18 November 2022 – via PR Newswire.
  2. ^ a b "Tzield- teplizumab-mzwv injection". DailyMed. 17 November 2022. Retrieved 4 December 2022.
  3. ^ a b c "FDA Approves First Drug That Can Delay Onset of Type 1 Diabetes". U.S. Food and Drug Administration (Press release). 17 November 2022. Retrieved 18 November 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  4. S2CID 245451959
    . Retrieved 17 November 2022.
  5. ^ "Tzield (teplizumab-mzwv) approved by FDA as the first and only treatment indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients aged 8 years and older with stage 2 T1D" (Press release).
  6. S2CID 38982992
    .
  7. S2CID 26301557
    .
  8. PMID 16167085
    .
  9. ^ "Drug Approval Package: Tzield". accessdata.fda.gov. 5 January 2023. Retrieved 23 January 2023.
  10. ^ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration (FDA). 10 January 2023. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ New Drug Therapy Approvals 2022 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 14 January 2024. Retrieved 14 January 2024. Public Domain This article incorporates text from this source, which is in the public domain.
  12. PMID 9636555
    .
  13. PMID 16625825
    .
  14. PMID 21719095
    .
  15. ^ "MacroGenics, Lilly abandon diabetes drug". Washington Business Journal. 21 October 2010.
  16. ^ "MacroGenics sells rights for two autoimmune disorder candidates". The Pharma Letter.
  17. PMID 23835333
    .
  18. PMID 15919798
    .
  19. S2CID 36595661
    .
  20. S2CID 11868182
    .
  21. PMID 31180194
    .

External links

  • "Teplizumab". Drug Information Portal. U.S. National Library of Medicine.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Teplizumab&oldid=1195535759"