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09-12-2023 | Type 1 diabetes | News

Preservation of β-cell function with teplizumab in type 1 diabetes confirmed

Author: Sarah Pritchard


medwireNews: Teplizumab-mzwv consistently preserves the function of β-cells in people with type 1 diabetes to a significantly greater degree than standard care or placebo, as indicated by higher C-peptide levels at 1 and 2 years post-treatment, report researchers in Diabetes Care.

Their integrated efficacy analyses of five previous clinical trials of the humanized immunoglobulin G1 anti-CD3 monoclonal antibody in 609 patients with type 1 diabetes “provide robust evidence” confirming the drug’s ability to modify type 1 diabetes disease progression, by preserving β-cell function as well as reducing the use of exogenous insulin.

“These data provide the biologic foundation of a disease-modifying therapy for type 1 diabetes and further support teplizumab as a promising treatment that addresses the underlying autoimmune pathogenesis of type 1 diabetes,” write Laura Knecht, from Provention Bio, Inc. in New Jersey, USA, and colleagues.

The team examined changes from baseline in stimulated C-peptide levels, as a marker of β-cell function, plus exogenous insulin use, in individuals with stage 3 type 1 diabetes who received either teplizumab (n=375) or control treatment (either standard of care or placebo; n=234).

At both 1 and 2 years post-treatment, patients who had received the 14-day teplizumab regimen showed highly statistically significant improvements in C-peptide levels compared with their control counterparts. The least squares mean change in levels from baseline was 0.08 nmol/L greater at 1 year and 0.12 nmol/L greater at 2 years with teplizumab than the control treatment according to the observed data, and 0.09 nmol/L and 0.10 nmol/L greater, respectively, for imputed data.

Moreover, the decline in C-peptide levels from baseline to 1 year, following an initial increase with teplizumab in the first 6 months, was significantly less for those receiving the drug than for controls, at 8% and 27%, respectively. Corresponding results from studies with available 2-year data showed respective 34% and 51% declines, which were also significantly different.

“The results of the integrated analysis illustrate a significant difference in C-peptide preservation across multiple studies, supporting the consistency of the effects of teplizumab treatment across and within studies, suggesting that its biologic effects are robust, reproducible, and not unique to a specific study or patient characteristic,” remark Knecht et al.

Taking advantage of the trials’ ‘treat-to-target’ approach to diabetes management, the researchers also evaluated participants’ requirements for exogenous insulin. At 1 and 2 years post-treatment, teplizumab-treated patients used significantly less insulin than those given control treatments, by a corresponding least squares mean of 0.08 and 0.10 units/kg/day.    

Knecht and team also conducted an integrated safety analysis of 1018 patients with stage 2 or 3 type 1 diabetes from the trials, of whom 773 were randomly assigned to receive teplizumab and 245 to controls. After around 1500 person–years of follow up, almost all participants experienced self-limiting mild-to-moderate adverse effects (AEs) of grade 1 or 2 (mainly during or immediately after the dosing period), including lymphopenia, rash, or headache.

Serious AEs were reported in 12.4% of teplizumab-treated patients and 8.2% of controls, but most were not related to treatment. AEs leading to permanent discontinuation occurred in 14.3% and 3.7% of patients, respectively, and were mainly associated with laboratory investigations such as liver enzyme elevations and blood and lymphatic disorders.

The recent approval of teplizumab for delaying the onset of stage 3 type 1 diabetes in adults and children of at least 8 years of age with stage 2 disease, together with these additional analyses, “represents the first advance toward achieving the goal of developing disease-modifying therapies,” conclude the researchers.                                    

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group

Diabetes Care 2023; doi:10.2337/dc23-0675


Novel clinical evidence in continuous glucose monitoring

Novel clinical evidence in continuous glucose monitoring

How real-world studies complement randomized controlled trials

Jean-Pierre Riveline uses data from real-life continuous glucose monitoring studies to illustrate how these can uncover critical information about clinical outcomes that are hard to assess in randomized controlled trials.

This video has been developed through unrestricted educational funding from Abbott Diabetes Care.

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