Biosimilar Insulin Aspart Premix SAR341402 Mix 70/30 Versus Originator Insulin Aspart Mix 70/30 (NovoMix 30) in People with Diabetes: A 26-Week, Randomized, Open-Label Trial (GEMELLI M)

Abstract

Introduction This study compared the efficacy, safety, and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (SAR Asp -Mix) with European-approved insulin aspart mix 70/30 − NovoMix® 30 (NN-Mix) in people with type 1 (T1D) or type 2 diabetes (T2D). Methods This 26-week, open-label, phase 3 trial enrolled 402 people with T1D ( n = 105) or T2D ( n = 297) previously treated with premix insulin, who were randomized (1:1) to SAR Asp -Mix ( n = 204) or NN-Mix ( n = 198). Results After 26 weeks, the least squares (LS) mean [median] change in HbA1c from baseline was similar in both treatment groups (SAR Asp -Mix − 0.55% [− 0.60%]; NN-Mix − 0.64% [− 0.60%]). The LS mean difference for SAR Asp -Mix versus NN-Mix was 0.08%, with the upper bound of the two-sided 95% confidence interval (− 0.139 to 0.303) slightly above the prespecified noninferiority margin of 0.3%. Noninferiority of SAR Asp -Mix over NN-Mix was not demonstrated in the primary intent-to-treat analysis, primarily because of one extreme outlying value impacted by the COVID-19 pandemic in the SAR Asp -Mix group. Noninferiority was achieved in all secondary analyses, including prespecified per-protocol supportive and COVID-19 sensitivity analyses, as well as post hoc sensitivity analyses. Other efficacy endpoints, insulin dosages, anti-insulin aspart antibody response, hypoglycemia, and adverse events were similar between groups. Conclusions The totality of evidence indicates that SAR Asp -Mix provides effective glycemic control with a similar safety and immunogenicity profile to NN-Mix in people with diabetes treated for 26 weeks. Trial Registration EudraCT number 2017-000092-84. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-022-01255-7.

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

“…In GEMELLI M, adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) were pretreated with commercial premix NN-Mix or insulin lispro mix (Humalog Mix 25/Liprolog Mix 25, Eli Lilly) therapy. Results for the total study population following treatment for 26 weeks have been previously reported and confirm that SAR Asp -Mix and NN-Mix have similar efficacy, safety, and immunogenicity profiles [ 5 ].…”

“…Detailed methods of the trial have been previously reported [ 5 ]. In brief, GEMELLI M was a randomized, open-label, multinational, multicenter, active-controlled, parallel-group, phase 3 trial initiated in July 2019 and completed in August 2020.…”

“…The starting dose of SAR Asp -Mix or NN-Mix was a unit-to-unit (1:1) conversion from participants’ prestudy insulin dose at the end of the screening period, using the same frequency of administration. Premix doses were then titrated to achieve protocol‐specified glycemic targets, as reported previously [ 5 ].…”

“…At week 26, insulin dose values were reported as the median of daily doses available in the week prior to the study visit. Details on efficacy, safety, and immunogenicity outcomes have been previously reported [ 5 ].…”

“…Similarity of SAR-Asp and NN-Asp was initially demonstrated in physicochemical analyses and nonclinical studies. Phase 1 [ 4 ] and phase 3 (GEMELLI M) [ 5 ] trials were performed to confirm that SAR Asp -Mix and NN-Mix are highly similar. In GEMELLI M, adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) were pretreated with commercial premix NN-Mix or insulin lispro mix (Humalog Mix 25/Liprolog Mix 25, Eli Lilly) therapy.…”