Chemistry:Teplizumab

From HandWiki

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

Teplizumab's mechanism of action involves binding to CD3 protein complexes (a molecule involved in recognising antigens and activating T cells) on the surface of T-cells and modifying T-cell immune behaviour to reduce cytotoxicity.[4] This appears 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 T effector cells. In addition, regulatory cytokines are released and regulatory T cells are expanded that may lead to the reestablishment of immune tolerance. [5][6] To avoid overly stimulating cytokine release, the Fc region of this antibody has been engineered to have Fc receptor non-binding (FNB) properties.[4]

Teplizumab was approved for medical use in the United States in November 2022.[1][7] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[8][9]

Medical uses

Teplizumab is indicated to delay the onset of stage 3 type 1 diabetes in people aged eight years of age and older with stage 2 type 1 diabetes.[10][1]

History

Teplizumab was developed at the University of Chicago in partnership with Ortho Pharmaceutical, and was then further developed at MacroGenics, Inc.,[11][12] including a collaboration with Eli Lilly to conduct the first phase III clinical trial in early-onset type 1 diabetes.[13] After the initial Phase III trial conducted by Macrogenics failed to meet the primary endpoint,[14] the drug was acquired by Provention Bio, which restarted development based on subset analysis of the original trials.[15][16]

Society and culture

In November 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Teizeild, intended for the treatment of type 1 diabetes. The applicant for this medicinal product is Sanofi Winthrop Industrie.[17][18]

Research

Teplizumab has been used in clinical trials with the aim of protecting the remaining β-cells in people newly diagnosed with type 1 diabetes.[19] 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.[20]

Teplizumab has been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis.[21]

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.[22]

A systematic review and meta-analysis, published in 2024, found that use of teplizumab is associated with better preservation of circulating C-peptide levels.[23]

References

  1. ↑ 1.0 1.1 1.2 "FDA Approves First Drug That Can Delay Onset of Type 1 Diabetes". U.S. Food and Drug Administration (Press release). 17 November 2022. Archived from the original on 24 September 2023. Retrieved 18 November 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  2. ↑ American Diabetes Association Professional Practice Committee (January 2022). "2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022". Diabetes Care 45 (Suppl 1): S17–S38. doi:10.2337/dc22-S002. PMID 34964875. 
  3. ↑ "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).
  4. ↑ 4.0 4.1 "Anti-CD3 Antibody for the Prevention of Type 1 Diabetes: A Story of Perseverance". Biochemistry 58 (40): 4107–4111. October 2019. doi:10.1021/acs.biochem.9b00707. PMID 31523950. 
  5. ↑ "TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes". Nature Medicine 9 (9): 1202–1208. September 2003. doi:10.1038/nm924. PMID 12937416. 
  6. ↑ "TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs". The Journal of Clinical Investigation 115 (10): 2904–2913. October 2005. doi:10.1172/JCI23961. PMID 16167085. 
  7. ↑ "Drug Approval Package: Tzield". 5 January 2023. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/761183Orig1s000TOC.cfm. 
  8. ↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". 10 January 2023. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022.  Public Domain This article incorporates text from this source, which is in the public domain.
  9. ↑ (PDF) New Drug Therapy Approvals 2022 (Report). January 2024. https://www.fda.gov/media/164429/download. Retrieved 14 January 2024.  Public Domain This article incorporates text from this source, which is in the public domain.
  10. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Tzield FDA label
  11. ↑ "Humanized, nonmitogenic OKT3 antibody, huOKT3 gamma(Ala-Ala): initial clinical experience". Transplantation Proceedings 30 (4): 1369–1370. June 1998. doi:10.1016/S0041-1345(98)00278-4. PMID 9636555. 
  12. ↑ "Anti-CD3 antibody MacroGenics Inc". Current Opinion in Investigational Drugs 7 (4): 381–388. April 2006. PMID 16625825. 
  13. ↑ "Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial". Lancet 378 (9790): 487–497. August 2011. doi:10.1016/S0140-6736(11)60931-8. PMID 21719095. 
  14. ↑ "MacroGenics, Lilly abandon diabetes drug". Washington Business Journal. 21 October 2010. https://www.bizjournals.com/washington/quick_news/2010/10/macrogenics-lilly-abandon-diabetes-drug.html. 
  15. ↑ "MacroGenics sells rights for two autoimmune disorder candidates". The Pharma Letter. https://www.thepharmaletter.com/article/macrogenics-sells-rights-for-two-autoimmune-disorder-candidates. 
  16. ↑ "Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders". Diabetes 62 (11): 3766–3774. November 2013. doi:10.2337/db13-0345. PMID 23835333. 
  17. ↑ "Teizeild EPAR". 14 November 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/teizeild.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  18. ↑ "First-in-class treatment to delay onset of type 1 diabetes". 14 November 2025. https://www.ema.europa.eu/en/news/first-class-treatment-delay-onset-type-1-diabetes.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  19. ↑ "A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes". Diabetes 54 (6): 1763–1769. June 2005. doi:10.2337/diabetes.54.6.1763. PMID 15919798. 
  20. ↑ "Anti-CD3 mAbs for treatment of type 1 diabetes". Diabetes/Metabolism Research and Reviews 25 (4): 302–306. May 2009. doi:10.1002/dmrr.933. PMID 19319985. 
  21. ↑ "CD3-specific antibodies: a portal to the treatment of autoimmunity". Nature Reviews. Immunology 7 (8): 622–632. August 2007. doi:10.1038/nri2134. PMID 17641665. 
  22. ↑ "An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes". The New England Journal of Medicine 381 (7): 603–613. August 2019. doi:10.1056/nejmoa1902226. PMID 31180194. 
  23. ↑ "Role of Teplizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Managing Newly Diagnosed Type 1 Diabetes: An Updated Systematic Review and Meta-Analysis". Endocrine Practice 30 (5): 431–440. May 2024. doi:10.1016/j.eprac.2024.03.006. PMID 38519028. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Teplizumab&oldid=4243310"