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).

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

Conflict of interest statement

BS, CD, YR, PA, and AB are paid employees of Viatris Inc and may hold stock or stock options in the company. NS, AR, and SR are paid employees of Biocon Research Limited and may hold stock or stock options in the company. VW, ASR, and DP were employees of Biocon Research Limited during the time of the study and may hold stock or stock options in the company. RRB has served as a consultant for Viatris Inc.

Figures

Fig. 1

Study design of (a) INSTRIDE 1 and (b) INSTRIDE 2. T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus

Fig. 2

Fit plot of cross-reactive insulin antibody percent specific binding assays in (a) INSTRIDE 1 and (b) INSTRIDE 2

Fig. 3

a Mean change in cross-reactive ADA by visit using the MYL-1501D assay in INSTRIDE 1a and b actual median cross-reactive ADA by visit using the MYL-1501D assay in INSTRIDE 2.b ADA, antidrug antibodies; BL, baseline; %SB, percentage specific binding. aError bars represent the SD. bError bars represent the interquartile range

Fig. 4

Proportion of patients with a cross-reactive insulin antibody response using the MYL-1501D assay in (a) INSTRIDE 1 and (b) INSTRIDE 2

Fig. 5

Mean actual ECL ratio (anti-HCP antibodies) in (a) INSTRIDE 1 and (b) INSTRIDE 2. Error bars represent the SD. ECL ratio is defined as ECL/ECL at baseline. BL, baseline; ECL, enhanced electrochemiluminescence; HCP, host cell protein