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.
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