Similar immunogenicity profiles between the proposed biosimilar MYL-1501D and reference insulin glargine in patients with diabetes mellitus: the phase 3 INSTRIDE 1 and INSTRIDE 2 studies

BMC Endocr Disord. 2021 Jun 26;21(1):129. doi: 10.1186/s12902-021-00797-4.

Abstract

Background: MYL-1501D is a proposed biosimilar to insulin glargine. The noninferiority of MYL-1501D was demonstrated in patients with type 1 diabetes and type 2 diabetes in 2 phase 3 trials. Immunogenicity of MYL-1501D and reference insulin glargine was examined in both studies.

Methods: INSTRIDE 1 and INSTRIDE 2 were multicenter, open-label, randomized, parallel-group studies. In INSTRIDE 1, patients with type 1 diabetes received MYL-1501D or insulin glargine over a 52-week period. In INSTRIDE 2, patients with type 2 diabetes treated with oral antidiabetic drugs, insulin naive or not, received MYL-1501D or reference insulin glargine over a 24-week period. Incidence rates and change from baseline in relative levels of antidrug antibodies (ADA) and anti-host cell protein (anti-HCP) antibodies in both treatment groups were determined by a radioimmunoprecipitation assay and a bridging immunoassay, respectively. Results were analyzed using a mixed-effects model (INSTRIDE 1) or a nonparametric Wilcoxon rank sum test (INSTRIDE 2).

Results: Total enrollment was 558 patients in INSTRIDE 1 and 560 patients in INSTRIDE 2. The incidence of total and cross-reactive ADA was comparable between treatment groups in INSTRIDE 1 and INSTRIDE 2 (P > 0.05 for both). A similar proportion of patients had anti-HCP antibodies in both treatment groups in INSTRIDE 1 at week 52 (MYL-1501D, 93.9 %; reference insulin glargine, 89.6 %; P = 0.213) and in INSTRIDE 2 at week 24 (MYL-1501D, 87.3 %; reference insulin glargine, 86.9 %; P > 0.999).

Conclusions: In INSTRIDE 1 and INSTRIDE 2, similar immunogenicity profiles were observed for MYL-1501D and reference insulin glargine in patients with type 1 diabetes and type 2 diabetes, respectively.

Trial registration: ClinicalTrials.gov, INSTRIDE 1 ( NCT02227862 ; date of registration, August 28, 2014); INSTRIDE 2 ( NCT02227875 ; date of registration, August 28, 2014).

Keywords: Biosimilar; Diabetes mellitus; Immunogenicity; Insulin glargine; MYL-1501D.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biosimilar Pharmaceuticals / pharmacology
  • Biosimilar Pharmaceuticals / therapeutic use
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Immunogenetic Phenomena / drug effects*
  • Immunogenetic Phenomena / physiology
  • Insulin Glargine / pharmacology
  • Insulin Glargine / therapeutic use*
  • Male
  • Middle Aged

Substances

  • Biosimilar Pharmaceuticals
  • Hypoglycemic Agents
  • MYL-1501D
  • Insulin Glargine

Associated data

  • ClinicalTrials.gov/NCT02227862
  • ClinicalTrials.gov/NCT02227875