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.

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 1^a 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