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) (SARAsp-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 SARAsp-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 SARAsp-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 SARAsp-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 SARAsp-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.

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).

INTRODUCTION: This study compared the efficacy, safety, and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (SARAsp-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 SARAsp-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 (SARAsp-Mix - 0.55% [- 0.60%]; NN-Mix - 0.64% [- 0.60%]). The LS mean difference for SARAsp-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 SARAsp-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 SARAsp-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 SARAsp-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.

Safety and efficacy of GP40061 compared with originator insulin glargine (Lantus®): a randomized open-label clinical trial.

Aim: To compare safety (immunogenicity) and efficacy of GP40061 insulin glargine (GP-Gla) and Lantus® (Sanofi glargine, Sa-Gla) in people with diabetes mellitus. Materials & methods: This randomized open-label, 26-week clinical trial enrolled 180 Type 1 diabetes mellitus patients (HbA1c 6.5-12.0%), randomized 1:1 to once daily GP-Gla (n = 90) or Sa-Gla (n = 90). The primary end point was immune response at 26th week. Results: The frequency of immune response was similar in GP-Gla and Sa-Gla (p = 1.000). Groups were similar in terms of other safety end points. Mean HbA1c change from baseline was -0.66% for GP-Gla and -0.77% for Sa-Gla, and did not differ between groups (p = 0.326). Insulin doses, fasting plasma glucose and seven-point glucose profiles were similar between groups. Conclusion: GP-Gla and Sa-Gla demonstrated similar safety and efficacy. ClinicalTrials.gov Identifier: NCT04022993.