Endocrine Abstracts

Introduction

A biosimilar is a biological medicinal product that shows high similarity to another already approved medicine product containing biotechnology-derived protein as active substance. The similarity depends on the biosimilar development program that includes comparative studies of physical and chemical properties, in vitro pharmacodynamics, pharmacokinetics and pharmacodynamics in humans. Insulin aspart biphasic 30 is one of the most convenient insulin formulations providing both prandial and basal insulin in a single injection. Russian biopharmaceutical company GEROPHARM has developed insulin aspart biphasic 30 that showed similarity to an originator NovoMix 30 FlexPen (NN-Asp30) in all abovementioned studies. The last stage of the biosimilar development program is comparative immunogenicity and efficacy study of insulin biosimilar and reference drug. Therefore, the aim of this study was to compare the immunogenicity and the efficacy of insulin aspart biphasic 30 (GP40081 (GP-Asp30)) with originator insulin NN-Asp30.

Methods

This was a multicenter, randomized, open-label, active-controlled, non-inferiority phase 3 clinical trial in parallel groups, conducted in order to compare safety (immunogenicity) and efficacy of GP-Asp30 with these parameters of NN-Asp30. This 26-week clinical trial enrolled 264 participants with type 2 diabetes mellitus (HbA1c 7.6–12.0%), randomized 1:1 to once-daily GP-Asp30 (n = 132) or NN-Asp30 (n = 132). The primary safety endpoint was immune response (development of anti-insulin antibodies (AIA)) at week 26. Secondary immunogenicity endpoints included the change of mean AIA concentration from baseline to weeks 12 and 26, the formation of neutralizing antibodies and clinically significant immune response at week 26. Efficiency endpoints included HbA1c change at week 26 from baseline, change of fasting plasma glucose (FPG) at week 26 from baseline and change in seven-point glucose profile (SPGP). Non-inferiority margin for HbA1c was 0.4 %.

Results

The frequency of immune response was similar in GP-Asp30 and NN-Asp30 (PP-population) both at week 12 (P = 0.107), and at week 26 (P = 1.000). The change of mean AIA concentration was not also significantly different in GP-Asp30 and NN-Asp30 (ITT-population) both at week 12 (P = 0.191), and at week 26 (P = 0.435). The frequency of clinically significant immune response was similar in GP-Asp30 and NN-Asp30 (P = 0.861 for ITT-population, P = 0.858 for PP-population). Inter-group difference of HbA1c change at week 26 was 0.12 (95% CI [-0.14, 0.38]). FPG, SPGP and insulin dose were similar between the groups.

Conclusions

GP-Asp30 and NN-Asp30 demonstrated similar safety (immunogenicity) and efficacy.