Efficacy and safety of MYL‐1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: Results of the INSTRIDE 1 phase III study

Abstract

The upper 95% CI limit for mean change in HbA1c at week 24 indicated that MYL-1501D was non-inferior to reference insulin glargine. There were no clinically meaningful differences between groups in incidence of overall and nocturnal hypoglycaemia, local or systemic reactions, safety or immunogenicity.

Efficacy and safety of MYL‐1501D versus insulin glargine in people with type 1 diabetes mellitus: Results of the INSTRIDE 3 phase 3 switch study

“…Changes from baseline in terms of the incidence of TEAR were similar between the treatment‐switching and reference insulin glargine treatment sequences. These results suggest that both insulin glargine preparations demonstrated similar immunogenic potential, and switching patients from MYL‐1501D to reference insulin glargine and back to MYL‐1501D did not impact immunogenicity; these results further confirm the similar safety profiles of MYL‐1501D and reference insulin glargine demonstrated in earlier studies . The TEAR findings of the present study were similar to the immunogenicity and safety results of a study comparing another insulin glargine biosimilar (LY2963016) and reference insulin glargine in which the proportion of participants with detectable TEAR was similar between treatment groups, providing additional evidence to support the development and use of biosimilars or FOBs for therapeutics such as insulin …”

“…Although there were numerically more nocturnal hypoglycaemic events in the MYL‐1501D treatment sequence compared with the reference insulin glargine treatment sequence, this trend was probably not related to treatment because the trend was consistent across all three treatment periods, including when participants were receiving reference insulin glargine. Overall, the safety results support the safety results of INSTRIDE 1 and INSTRIDE 2 and indicate that the two sequence groups in the present study had equivalent safety profiles throughout the study at the end of the treatment period, and switching treatments had no impact on TEAEs, hypoglycaemic events, immunogenicity profiles, or other safety variables.…”

“…This was a multicentre, open‐label, randomized, parallel‐group, phase 3 study comparing the efficacy and safety of MYL‐1501D with those of US‐sourced reference insulin glargine (Lantus) in patients with T1DM (http://clinicaltrials.gov identifier: NCT02666430). Individuals who successfully completed 52 weeks of reference insulin glargine treatment in the INSTRIDE 1 study (NCT02227862) and provided written informed consent were eligible. Individuals were excluded if they had a history of clinically significant infections, had moderate insulin resistance (requiring basal plus prandial insulin of ≥1.5 U/kg/d), or planned to receive elective surgery requiring hospitalization or another investigational drug during the study period.…”

“…MYL‐1501D, which has an amino acid sequence identical to that of reference insulin glargine, has recently been approved by the EMA as a biosimilar and is being developed as an FOB to insulin glargine in the United States. Determination of biosimilarity was based in part on the results of two phase 3 studies, INSTRIDE 1 and INSTRIDE 2, which demonstrated similar safety and efficacy of MYL‐1501D and reference insulin glargine in patients with T1DM and type 2 diabetes mellitus, respectively (http://clinicaltrials.gov identifiers: NCT02227862 and NCT02227875, respectively) . The primary objective of the INSTRIDE 3 study was to assess whether patients with T1DM can switch between MYL‐1501D and reference insulin glargine through testing equivalence after 36 weeks between two treatment sequences (ie, patients who remain on reference insulin glargine vs. those who switch between MYL‐1501D and reference insulin glargine).…”

Biosimilar vs originator insulins: Systematic review and meta‐analysis

“…Among 405 candidate studies identified from electronic databases and other sources, 10 randomized trials (4935 patients) were assessed, including 8 studies on long-acting biosimilar insulins [11][12][13][14][15][16][17][18] (2 each on LY2963016, MK-1293 and Mylan's insulin glargine, and 1 each on FFP-112 and Basalog: 3923 patients) and 2 studies on short-acting biosimilar insulin 19,20 (both on SAR342434 insulin lispro: 1012 patients; Appendix S4).…”