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Teplizumab: First Approval

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Abstract

Teplizumab (teplizumab-mzwv; TZIELD™) is a CD3-directed monoclonal antibody (humanized IgG1κ) that is being developed by Provention Bio, Inc. for the treatment of type 1 diabetes (T1D). In November 2022, teplizumab was approved in the USA to delay the onset of Stage 3 T1D in adults and pediatric patients 8 years of age and older with Stage 2 T1D, based on results of a clinical trial in high-risk relatives of individuals with T1D. This article summarizes the milestones in the development of teplizumab leading to this first approval in the treatment of T1D.

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References

  1. Rosen CJ, Ingelfinger JR. Traveling down the long road to type 1 diabetes mellitus prevention. N Engl J Med. 2019;381(7):666–7.

    Article  PubMed  Google Scholar 

  2. Bluestone JA, Buckner JH, Herold KC. Immunotherapy: building a bridge to a cure for type 1 diabetes. Science. 2021;373(6554):510–6.

    Article  CAS  PubMed  Google Scholar 

  3. Herold KC, Hagopian W, Auger JA, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002;346(22):1692–8.

    Article  CAS  PubMed  Google Scholar 

  4. Herold KC, Bundy BN, Long SA, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019;381(7):603–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aly TA, Ide A, Jahromi MM, et al. Extreme genetic risk for type 1A diabetes. Proc Natl Acad Sci USA. 2006;103(38):14074–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hemminki K, Li X, Sundquist J, et al. Familial association between type 1 diabetes and other autoimmune and related diseases. Diabetologia. 2009;52(9):1820–8.

    Article  CAS  PubMed  Google Scholar 

  7. Parkkola A, Harkonen T, Ryhanen SJ, et al. Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children. Diabetes Care. 2013;36(2):348–54.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Provention Bio Inc. TZIELD™ (teplizumab-mzwv): US prescribing information. 2022. https://tzield.com/. Accessed 13 Dec 2022.

  10. Woodle ES, Xu D, Zivin RA, et al. Phase I trial of a humanized, Fc receptor nonbinding OKT3 antibody, huOKT3γ1 (Ala-Ala) in the treatment of acute renal allograft rejection. Transplantation. 1999;68(5):608–16.

    Article  CAS  PubMed  Google Scholar 

  11. Provention Bio Inc. TZIELDTM (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 [media release]. 17 Nov 2022. http://www.proventionbio.com.

  12. US Food and Drug Administration. FDA approves first drug that can delay onset of type 1 diabetes [media release]. 17 Nov 2022. http://www.fda.gov.

  13. American Diabetes Association. Understanding A1C: diagnosis. 2023. http://diabetes.org/diabetes/a1c/diagnosis. Accessed 2 Feb 2023.

  14. Sanofi. Sanofi US enters into co-promotion agreement with Provention Bio, Inc. to launch teplizumab, an investigational disease-modifying therapy for type 1 diabetes [media release]. 6 Oct 2022. http://www.sanofi.com.

  15. Provention Bio Inc. Provention Bio to combine forces with Sanofi to support potential U.S. launch of teplizumab for delay in onset of clinical type 1 diabetes (T1D) in at-risk individuals [media release]. 6 Oct 2022. http://www.proventionbio.com.

  16. Provention Bio Inc. Provention Bio announces agreements with MacroGenics for two clinical-stage assets for the treatment of autoimmune disorders [media release]. 9 May 2018. http://www.proventionbio.com.

  17. Macrogenics Inc. Lilly and MacroGenics announce licensing and collaboration agreement [media release]. 18 Oct 2007. http://ir.macrogenics.com/.

  18. Eli Lilly and Company. Lilly reports fourth-quarter and full-year 2010 results, provides 2011 financial guidance [media release]. 27 Jan 2011. http://www.lilly.com.

  19. MacroGenics Inc. Promising treatment for juvenile diabetes advances with agreement signed by MacroGenics and Tolerance Therapeutics [media release]. 18 Jul 2005. http://ir.macrogenics.com/.

  20. Long SA, Thorpe J, DeBerg HA, et al. Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol. 2016. https://doi.org/10.1126/sciimmunol.aai7793.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sims EK, Bundy BN, Stier K, et al. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med. 2021. https://doi.org/10.1126/scitranslmed.abc8980.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sims EK, Cuthbertson D, Herold KC, et al. The deterrence of rapid metabolic decline within 3 months after teplizumab treatment in individuals at high risk for type 1 diabetes. Diabetes. 2021;70(12):2922–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sherry N, Hagopian W, Ludvigsson J, et al. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet. 2011;378(9790):487–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Herold KC, Gitelman SE, Ehlers MR, et al. 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. 2013;62(11):3766–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Long SA, Thorpe J, Herold KC, et al. Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes. Cell Immunol. 2017;319:3–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Perdigoto AL, Preston-Hurlburt P, Clark P, et al. Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia. 2019;62(4):655–64.

    Article  CAS  PubMed  Google Scholar 

  27. Herold KC, Gitelman SE, Willi SM, et al. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013;56(2):391–400.

    Article  CAS  PubMed  Google Scholar 

  28. Hagopian W, Ferry RJ, Sherry N, et al. Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial. Diabetes. 2013;62(11):3901–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Provention Bio Inc. Provention Bio provides update on the status of its phase 3 PROTECT study for the treatment of newly diagnosed type 1 diabetes [media release]. 16 Mar 2020. http://www.proventionbio.com.

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    Susan J. Keam

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  1. Susan J. Keam
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Correspondence to Susan J. Keam.

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The preparation of this review was not supported by any external funding.

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During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Susan J. Keam is a contracted employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

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Keam, S.J. Teplizumab: First Approval. Drugs 83, 439–445 (2023). https://doi.org/10.1007/s40265-023-01847-y

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