Mylan’s insulin glargine follow-on, MYL-1501D, referencing Sanofi’s Lantus, is a long-acting human insulin analogue that allows for once-daily basal use in patients with type 1 diabetes. The drug has been authorized for marketing as a biosimilar insulin in the European Union and in Australia under the brand name Semglee.
Mylan’s insulin glargine follow-on, MYL-1501D, referencing Sanofi’s Lantus, is a long-acting human insulin analogue that allows for once-daily basal use in patients with type 1 diabetes (T1D). The drug has been authorized for marketing as a biosimilar insulin in the European Union and in Australia under the brand name Semglee.
Writing in Diabetes, Obesity, and Metabolism with full data that were previously presented in part at the American Diabetes Associations’ 77th Scientific Sessions, researchers delivered results of the INSTRIDE 1 study, a 52-week, open-label, randomized, phase 3 study that sought to demonstrate whether once-daily MYL-1501D was noninferior, in terms of change in glycated hemoglobin (A1C) from baseline to week 24, to once-daily reference insulin glargine when administered with mealtime insulin lispro in patients with T1D.
In total, 558 patients were randomized 1:1 to receive either the investigational drug or the reference in combination with mealtime insulin lispro for the 52-week treatment period. In total, 93% of the patients (n = 261) in the follow-on group and 92.1% of patients (n = 256) in the reference group completed the full study.
The mean change in A1C from baseline to week 24 was 0.14% (standard error [SE], 0.054; 95% CI, 0.033-0.244) for the follow-on group, and 0.11% (SE, 0.054; 95% CI, 0.007-0.220) for the reference group, and the least squares (LS) mean difference in change in A1C from baseline to week 24 between the 2 treatment groups was 0.03% (SE, 0.046; 95% CI −0.066-0.117). The upper bound of the 95% CI fell within the predefined inferiority margin of 0.4% at week 24.
At week 52, the mean change in A1C from baseline was 0.21% (SE, 0.055; 95% CI, 0.100-0.306) and 0.25% (SE, 0.056; 95% CI, 0.144-0.363) for the 2 groups, respectively, and the LS mean difference in change in A1C for the 2 groups was −0.05% (SE, 0.052; 95% CI, −0.148-0.057).
Fasting plasma glucose was consistent in the 2 treatment groups at weeks 12, 36, and 52. A slight increase in weight was observed in both groups at week 52, but no significant difference was observed between the groups. Basal daily insulin dose also increased in both groups, with no significant differences in the change from baseline in total daily insulin dose observed.
Rates of treatment-emergent adverse events (TEAEs) were similar between the groups at week 52; in total, 225 patients (80.4%) in the follow-on group and 239 patients (86.0%) in the reference group experienced at least 1 TEAE during the 52-week period. The most common TEAE was hypoglycemia, followed by upper respiratory tract infection and nasopharyngitis. During the study, 2 patients in the follow-on arm died (1 death was of an unknown cause and was deemed unrelated to the study drug, and 1 was due to hypoglycemia), while 1 patient in the reference group died (due to myocardial infarction that was deemed unrelated to the reference drug).
The number of patients with 1 or more local and systemic reaction during the treatment period was similar between the 2 arms, and no statistically significant differences between the 2 treatment groups were observed for any type of insulin antibodies at any visit during the treatment period.
The researchers conclude that the study met its primary endpoint of noninferiority in terms of change in A1C, and that there were no significant treatment differences observed in the 2 groups in secondary measures, and that the follow-on was well tolerated, and no new or significant safety issues were observed.
Blevins TC, Barve A, Sun B, Ankersen M. Efficacy and safety of MYL-1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: results of the INSTRIDE 1 phase 3 study [published online April 15, 2018]. Diabetes Obes Metab. doi: 10.1111/dom .13322.