Immunogenicity of LY2963016 insulin glargine and Lantus® insulin glargine in Chinese patients with type 1 or type 2 diabetes mellitus

Abstract

Aims To evaluate the immunogenicity of LY2963016 insulin glargine (LY IGlar) versus originator insulin glargine (IGlar [Lantus®]) in Chinese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). Materials and Methods ABES and ABET were prospective, randomized, active control, open‐label, phase III studies, which enrolled Chinese patients with T1DM (N = 272) and T2DM (N = 536), respectively. Using data from these trials, immunogenicity of LY IGlar and IGlar was evaluated by comparing the proportion of patients with detectable anti‐insulin glargine antibodies and the median antibody levels (percent binding) between the treatment groups. The incidence of anti‐insulin antibodies and treatment‐emergent antibody response (TEAR) were compared using Fisher's exact test or Pearson's chi‐squared test. Levels of anti‐insulin antibodies were compared using the Wilcoxon rank‐sum test. We also evaluated the relationship between antibody formation or TEAR and clinical outcomes using analysis of covariance, negative binomial regression, or partial correlations. Results There were no significant treatment differences in the incidence of detectable anti‐insulin antibodies, median antibody levels or TEAR, overall or at Week 24 with last observation carried forward, and median antibody levels were low (<5%) after 24 weeks of treatment, in patients with T1DM or T2DM. Levels of anti‐insulin antibodies and development of TEAR were not associated with efficacy (glycated haemoglobin, insulin dose [U/kg/d] and hypoglycaemia) or safety outcomes. Conclusions The immunogenicity profiles of LY IGlar and IGlar are similar, with low levels of anti‐insulin antibodies observed for both insulins. No association was observed between antibody levels or TEAR status and clinical outcomes.

Toward once-monthly insulin therapy via synergy in two pharmacokinetic protractors: Fc-conjugation and fatty acid acylation

“…Another concern comes from the dog study where we observe the development of anti-drug antibodies (ADAs). 49,50 However, given that both the insulin and Fc components are based on human sequences, it is uncertain whether a similar immune response will occur in human subjects. Efsitora alfa that incorporates human Fc protein in its design did not show any issues with ADA formation in clinical studies.…”