Background: MYL-1501D is a long-acting human insulin analogue with amino acid sequence, strength, and formulation identical to the reference product (insulin glargine), although both are manufactured using different recombinant host cells and purified via distinct processes. INSTRIDE 1 was a multicenter, open-label, randomized, parallel-group, phase 3 study comparing the efficacy and safety of proposed biosimilar MYL-1501D with reference insulin glargine in patients with type 1 diabetes mellitus (T1DM).  
Aims: This analysis examined immunogenicity profiles in patients from INSTRIDE 1. 
Method: Immunogenicity was compared between the MYL-1501D and reference insulin glargine groups. Assessments included incidence and change from baseline in the relative levels of antidrug antibodies (ADA). Total and insulin cross-reactive ADA were reported in terms of percent specific binding (% SB). Exploratory analysis for possible antibody neutralization effect was also performed, which was defined as ADA >10%, increase in glycosylated hemoglobin (HbA1c) >0.2%, and increase in total insulin dose.
Results: In patients with T1DM (N=558), change from baseline in ADA % SB profiles was similar in the MYL-1501D (n=280) and reference insulin glargine (n=278) groups, and there were no statistically significant differences through week 52. The proportion of patients who met the criteria for a total ADA response (% SB ≥1.15%) was not statistically different between the treatment groups at all time points (MYL-1501D: 69.3% and 67.1%; reference insulin glargine: 70.9% and 66.5% at weeks 24 and 52, respectively). Incidence of positive neutralization effect was generally low (≤10%) and comparable in MYL-1501D–treated and insulin glargine–treated patients (5.4%, 8.9%, and 10.0% vs 6.1%, 6.5%, and 7.9% at weeks 24, 36, and 52, respectively). 
Discussion: The immunogenicity profiles were similar between the MYL-1501D and reference insulin glargine groups in patients with T1DM in INSTRIDE 1. Consistent with previous studies indicating an increased prevalence of insulin antibodies in patients with T1DM,1 a majority of patients were positive for total ADA. Neutralization of insulin activity by ADA appeared to be rare.

Comparable immunogenicity between proposed biosimilar MYL-1501D and insulin glargine in the INSTRIDE 1 study