Journal Article

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

Ramaswamy, Shilpa, Bowsher, Ronald R., Roy, Arnab Sinha, Donnelly, Charles, Pathak, Divya, Sengupta, Nilanjan, Waichale, Vinit, Barve, Abhijit, Sun, Bin, Raiter, Yaron, Rao, Anita, Aubonnet, Patrick

2021

Overview

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).

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Analysis / Antibodies / Antidiabetics / Biological products / Biosimilar / Biosimilar Pharmaceuticals - pharmacology / Biosimilar Pharmaceuticals - therapeutic use / Care and treatment / Clinical trials / Diabetes / Diabetes mellitus / Diabetes mellitus (insulin dependent) / Diabetes mellitus (non-insulin dependent) / 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 / Diabetes therapy / Diabetics / Drug dosages / Endocrinology / Ethics / Fasting / Female / Glucose / Humans / Hyperglycemia / Hypoglycemic Agents - pharmacology / Hypoglycemic Agents - therapeutic use / Immunogenetic Phenomena - drug effects / Immunogenetic Phenomena - physiology / Immunogenicity / Insulin / Insulin glargine / Insulin Glargine - pharmacology / Insulin Glargine - therapeutic use / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Metabolic Diseases / Middle Aged / MYL-1501D / Patients / Peptides / Rankings / rology / Type 2 diabetes / Viral antibodies