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

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).

Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study

“…35 The proportion of treatment-induced AIA in patients with T2DM in this study was similar to that reported in other studies (approximately 20%) but lower than in patients with T1DM (approximately 60%). 36 This discrepancy may be because of the differences in the immune response in patients with T1DM and T2DM, which may affect their respective immunogenicity profiles. 36 In addition, the majority of patients with T1DM were already treated with exogenous insulin therapy before entering clinical trials.…”

“…36 This discrepancy may be because of the differences in the immune response in patients with T1DM and T2DM, which may affect their respective immunogenicity profiles. 36 In addition, the majority of patients with T1DM were already treated with exogenous insulin therapy before entering clinical trials. Therefore, as expected, the baseline presence of detectable anti-insulin antibodies was higher in patients with T1DM than in insulin-naïve patients with T2DM.…”

Biosimilar of analogue of insulin glargin: proven safety, effectiveness, interchangeability

“…Available at: https://www.cochranelibrary.com/search. ных гипогликемий, локальных и генерализованных реакций, иммунобезопасности [23,24].…”

Understanding Biosimilar Insulins - Development, Manufacturing, and Clinical Trials

“…74 Both Semglee and Abasaglar have undergone the required human PK/PD and immunogenicity studies, meeting criteria for clinical biosimilarity. 80 -87…”

“…74 Both Semglee and Abasaglar have undergone the required human PK/PD and immunogenicity studies, meeting criteria for clinical biosimilarity. [80][81][82][83][84][85][86][87] Admelog (insulin lispro) and SAR-Asp (insulin aspart) were developed by Sanofi as biosimilars to Humalog (Eli Lilly) and NovoRapid/NovoLog (NovoNordisk). Approvals were granted for the former in the European Union as a biosimilar and in the United States as follow-on insulin in 2017 and for the latter in the European Union as a biosimilar in 2020.…”