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Efficacy and Safety of MK-1293 Insulin Glargine Compared with Originator Insulin Glargine (Lantus®) in Type 1 Diabetes
MK-1293 is a biosimilar insulin glargine under development using insulin glargine (Lantus®) as the originator benchmark. Compared to Lantus, it uses the same amino acid sequence, said Philip Home, MD, PhD, Newcastle, UK, the same production cell type (E. coli) and the same pharmaceutical formulation. Previous American Diabetes Association (ADA) presentations have confirmed MK-1293’s similar pharmacokinetic and pharmocodynamic properties and efficacy in both type 1 and type 2 diabetes, Dr. Home said in his oral presentation at the 2016 ADA Annual Meeting.
Dr. Home’s 52-week phase 3, active-controlled, open-label (re-usable pen injectors) comparison (with primary endpoints at 24-weeks) enrolled 506 subjects with type 1 diabetes (HbA1c ≤11.0%) taking basal (once-daily) and prandial insulin, and randomized them 1:1 to MK-1293 or Lantus® guided by a fasting glucose-based dosing algorithm.
The primary efficacy endpoint was non-inferiority of change from baseline of HbA1c (margin of <0.40 %). The primary safety objective was anti-insulin antibody (AIA) development.
The primary self-monitored fasting plasma glucose (SMFPG) target was 70-100 mg/dl).
Mean age of included patients was 42 years (~57.5% male), with an average type 1 diabetes disease duration of ~22 years. Mean HbA1c was 8.0%.
Change from baseline at 24 weeks was -0.65 (-0.82, -0.48) for MK-1293 and -0.68 (-085, -0.52) for Lantus®, a difference of 0.03 (-0.12, 0.18). Twenty-four week analysis of HbA1c revealed a difference of 0.04% (95% CI -0.11, 0.19), with 37.0% of individuals receiving MK-1293 and 37.7% of those receiving Lantus® meeting the <7.0% goal (-0.8 [-9.7, 8.1]). The <6.5% HbA1c goal was met by 20.5% of those receiving MK-1293 and by 21.6% of those in the Lantus® group (-1.1 [-8.6, 6.5]). Differences were not statistically significant.
Differences in other measures were similarly not significant (fasting plasma glucose change, 7-point average self-monitored plasma glucose, hypoglycemia events). A higher rate (events/person-years) of severe hypoglycemic events with MK-1293 (6.1 versus 3.2) was attributed to two patients at the same center accounting for 49% of severe episodes.
Immunological adverse events and cumulative incidence of anti-insulin antibodies over 12 and 24 weeks were low and similar between groups. No relationship could be discerned between antibody positivity, antibody titre, or neutralizing antibody positivity with HbA1c or insulin dose, either for the population or in any individual. “There were so few immune events that you could say that there is no signal for any immunological problem with MK-1293,” Dr. Home commented.
He concluded, “The overall therapeutic profile of MK-1293 was similar to that of Lantus® in people with type 1 diabetes over 24 weeks.”
Dr. Home also criticized the demand by regulatory bodies for clinic measures in type 1 diabetes trials. “I think the underlying metric is completely invalid, because people with type 1 diabetes are never fasting…personally, I prefer the self-monitored approach, but regulators won’t allow that.”