Efficacy and Safety of Insulin Aspart Biosimilar SAR341402 Versus Originator Insulin Aspart in People with Diabetes Treated for 26 Weeks with Multiple Daily Injections in Combination with Insulin Glargine: A Randomized Open-Label Trial (GEMELLI 1)

Abstract

Background: This study compared the efficacy, safety, and immunogenicity of insulin aspart biosimilar/followon biologic product SAR341402 (SAR-Asp) with originator insulin aspart-NovoLog Ò /NovoRapid Ò (NN-Asp) in people with type 1 diabetes (T1D) or type 2 diabetes (T2D) treated with multiple daily injections in combination with insulin glargine (Lantus Ò ; Gla-100). Materials and Methods: This 6-month, randomized, open-label, phase 3 study (NCT03211858) enrolled 597 people with T1D (n = 497) or T2D (n = 100). Participants were randomized 1:1 to mealtime SAR-Asp (n = 301) or NN-Asp (n = 296) in combination with Gla-100. The primary objective was to demonstrate noninferiority (by 0.3% margin in the intent-to-treat population) of SAR-Asp versus NN-Asp in HbA1c change from baseline to week 26. Immunogenicity was also assessed in terms of anti-insulin aspart antibody (AIA) status (positive/negative) and titers during the study. Results: HbA1c was similarly improved in both treatment groups (SAR-Asp-0.38%; NN-Asp-0.30%); the least squares mean difference at week 26 for SAR-Asp minus NN-Asp was-0.08% (95% confidence interval:-0.192 to 0.039), thus meeting the criteria for noninferiority between SAR-Asp and NN-Asp and inverse noninferiority of NN-Asp versus SAR-Asp. Changes in fasting plasma glucose and seven-point self-monitored plasma glucose profile, including postprandial glucose excursions, and insulin dosages were similar in both groups at week 26. Safety and tolerability, including AIA responses (incidence, prevalence), hypoglycemia, and adverse events (including hypersensitivity events and injection site reactions), were similar between groups. Conclusions: SAR-Asp demonstrated effective glycemic control with a similar safety and immunogenicity profile to NN-Asp in people with diabetes treated for 26 weeks.

Safety, Immunogenicity, and Glycemic Control of Insulin Aspart Biosimilar SAR341402 Versus Originator Insulin Aspart in People with Diabetes Also Using Insulin Glargine: 12-Month Results from the GEMELLI 1 Trial

“…Details of the study design have been previously described. 8 Briefly, participants ‡18 years of age with T1D or with T2D (in the United States only) on insulin treatment for at least 1 year were randomized 1:1 to receive SAR-Asp or NN-Asp for a period of 12 months.…”

“…The major exclusion criteria for participants with T1D and T2D have been previously described. 8 Participants randomized to NN-Asp received US-approved NN-Asp (NovoLog) in the United States or EU-approved NN-Asp (NovoRapid) in other countries, including Japan. Based on the similarity between NN-Asp-US and NN-Asp-EU shown in prior studies, 7 data from both forms of insulin were pooled in the comparator group.…”

“…Details of treatment regimens have been previously described. 8 Mealtime insulin was titrated to a 2-h postprandial plasma glucose (PPG) level of <180 mg/dL (<10 mmol/L) while avoiding hypoglycemia or a preprandial target range of 80-130 mg/dL (4.4-7.2 mmol/L). 9 Gla-100 was injected once daily and titrated to a fasting prebreakfast selfmonitored plasma glucose (SMPG) level of 80-130 mg/dL (4.4-7.2 mmol/L), while avoiding hypoglycemia.…”

“…Details of the assessments have been previously described. 8 The efficacy outcomes in this analysis included change in HbA1c from baseline to week 52, the percentage of study participants with HbA1c <7.0% (<53 mmol/mol) at week 52, change from baseline to week 52 in laboratory-measured fasting plasma glucose (FPG) and in mean 24-h plasma glucose concentration and PPG excursions (based on the seven-point SMPG profiles), and mean change from baseline to week 52 in seven-point SMPG profiles per time point (based on measurements taken before and 2 h after breakfast, lunch, and dinner, and at bedtime).…”

“…The 6-month GEMELLI 1 results demonstrated equivalent glycemic control with SAR-Asp and NN-Asp, associated with a similar safety and immunogenicity profile. 8 We now report the 12-month safety, immunogenicity, and efficacy results from GEMELLI 1.…”