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. 2023 Oct 1;46(10):1848-1856.
doi: 10.2337/dc23-0675.

Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves β-Cell Function

Kevan C Herold  1 , Stephen E Gitelman  2 , Peter A Gottlieb  3 , Laura A Knecht  4 , Ralph Raymond  4 , Eleanor L Ramos  4
Affiliations

Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves β-Cell Function

Kevan C Herold et al. Diabetes Care. .

Abstract

Objective: In November 2022, teplizumab-mzwv became the first drug approved to delay the onset of stage 3 type 1 diabetes in adults and children age ≥8 years with stage 2 type 1 diabetes on the basis of data from the pivotal study TN-10.

Research design and methods: To provide confirmatory evidence of the effects of teplizumab on preserving endogenous insulin production, an integrated analysis of C-peptide data from 609 patients (n = 375 patients receiving teplizumab and n = 234 control patients) from five clinical trials in stage 3 type 1 diabetes was conducted.

Results: The primary outcome of the integrated analysis, change from baseline in stimulated C-peptide, was significantly improved at years 1 (average increase 0.08 nmol/L; P < 0.0001) and 2 (average increase 0.12 nmol/L; P < 0.0001) after one or two courses of teplizumab. An analysis of exogenous insulin use was also conducted, showing overall reductions of 0.08 (P = 0.0001) and 0.10 units/kg/day (P < 0.0001) at years 1 and 2, respectively. An integrated safety analysis of five clinical trials that enrolled 1,018 patients with stage 2 or 3 type 1 diabetes (∼1,500 patient-years of follow-up for teplizumab-treated patients) was conducted.

Conclusions: These data confirm consistency in the preservation of β-cell function, as measured by C-peptide, across multiple clinical trials. This analysis showed that the most common adverse events included lymphopenia, rash, and headache, a majority of which occurred during and after the first few weeks of teplizumab administration and generally resolved without intervention, consistent with a safety profile characterized by self-limited adverse events after one or two courses of teplizumab treatment.

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Conflict of interest statement

Duality of Interest. This analysis was funded by Provention Bio, Inc., a Sanofi company (Red Bank, NJ). Editorial support was provided by ClinicalMind, LLC (New York, NY), and PharmaWrite, LLC (Princeton, NJ), and was funded by Provention Bio, Inc. K.C.H. has served as a consultant to Provention Bio, Inc., and is an inventor on a patent for the use of teplizumab for the delay of stage 3 type 1 diabetes but has declined royalties. S.E.G. has been a paid investigator for clinical trials sponsored by Provention Bio, Inc. P.A.G. has received funding from and served as a consultant to Provention Bio, Inc. No authors have been financially compensated for this manuscript. L.A.K., R.R., and E.L.R. are employees of Provention Bio, Inc., a Sanofi Company. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Forest plot of LSM differences in the change from baseline in C-peptide AUC between teplizumab and control groups. A: Analysis includes the five clinical trials with 1-year data. Analysis is with and without the imputed data for missing values. B: Analysis includes the three clinical trials for which 1- and 2-year data were available. Analysis is with and without the imputed data for missing values.
Figure 2
Figure 2
Mean (SE) observed C-peptide and insulin use from the clinical trials. A: C-peptide AUC levels at 1 year from the five studies with 1-year data. P value at 1 year was derived from the ANCOVA model for the 1-year integrated observed data. B: C-peptide AUC levels at 2 years from the three studies with 2-year data. P value at 2 years was derived from ANCOVA for the observed 2-year integrated data. C: Average insulin use at 1 year. P value at 1 year was derived from ANCOVA for the observed 1-year integrated data. D: Average insulin use at 2 years. P value at 2 years was derived from ANCOVA for the observed 2-year integrated data.
Figure 3
Figure 3
Forest plot of LSM differences in the change from baseline in insulin use between teplizumab and control groups. A: Analysis includes the five clinical trials with 1-year data. Analysis is with and without the imputed data for missing values. B: Analysis includes the three clinical trials for which 1- and 2-year data were available. Analysis is with and without the imputed data for missing values.
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