Efficacy, Safety, and Immunogenicity of Biosimilar Insulin Aspart Premix SAR341402 Mix 70/30 Compared with Originator Insulin Aspart Mix 70/30 in Adults with Diabetes (GEMELLI M): A Subgroup Analysis by Prior Type of Premix Insulin

Introduction We compared the efficacy, safety, and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (70% intermediate SAR341402 protamine and 30% rapid SAR341402 solution) (SAR Asp -Mix) with its originator NovoMix 30 insulin aspart mix (NN-Mix) in adults with type 1 or type 2 diabetes switching from different premix insulin analogs. Methods This phase 3, randomized, open-label, multinational, 26-week trial (GEMELLI M) enrolled 402 participants with type 1 or type 2 diabetes. At randomization, participants switched from their prestudy premix insulin NovoMix 30 ( n = 341) or Humalog Mix 25/Liprolog Mix 25 ( n = 61) to equivalent (1:1) doses of either SAR Asp -Mix or NN-Mix at least twice daily (1:1 randomization). In this subgroup analysis, efficacy measures [change in hemoglobin A1c (HbA1c), daily insulin dose], and safety outcomes [hypoglycemia incidence, adverse events (including hypersensitivity and injection site reactions), anti-insulin aspart antibodies] of SAR Asp -Mix were compared with those of NN-Mix separately according to the participants’ prestudy premix insulin. Results At week 26, change from baseline in HbA1c (primary efficacy endpoint) was similar between SAR Asp -Mix and NN-Mix in those participants pretreated with NovoMix 30 [least squares (LS) mean difference 0.05%, 95% confidence interval (CI) −0.195% to 0.289%] or Humalog Mix 25/Liprolog Mix 25 (LS mean difference 0.28%, 95% CI −0.279% to 0.830%) ( P value for treatment-by-subgroup interaction = 0.46). In both subgroups, safety outcomes, including immunogenicity, and changes in daily insulin doses were similar between treatments over 26 weeks. Conclusions Efficacy, safety, and immunogenicity profiles of SAR Asp -Mix are similar to NN-Mix over 26 weeks in adults with diabetes irrespective of prior type of premix insulin. Trial Registration EudraCT number 2017-000092-84.