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/follow-on biologic product SAR341402 (SAR-Asp) with originator insulin aspart-NovoLog®/NovoRapid® (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®; 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.

Keywords: Biosimilar; Follow-on product; GEMELLI 1; Insulin aspart; SAR341402.

Conflict of interest statement

S.K.G., Advisory Boards Consulting fees: Medtronic, Roche, Lexicon, Novo Nordisk, Sanofi, Eli Lilly, Zealand Pharmaceuticals, AstraZeneca. Research Grants: Eli Lilly, Novo Nordisk, Merck, Lexicon, Medtronic, Boehringer Ingelheim, NCI, T1D Exchange, NIDDK, JDRF, Sanofi. No stocks or equity in any device or pharmaceutical company. K.W.-P., M.W., D.K. and B.M., employees and stockholders of Sanofi. F.D., employee of Ividata. V.N.S., VNS' employer has received research funding from Type 1 Diabetes Exchange Registry (Jaeb Center for Health Research), National Institute of Health (NIDDK, NIAMS), Sanofi US, Dexcom, Inc., NovoNordisk, Eyenuk, Mylan GmbH, and vTv Therapeutics. V.N.S. has served on an advisory board for Sanofi US and consulted Dexcom, Inc. in the past. E.F., Advisory Boards Consulting Fees: Boehringer-Ingelheim, Novartis, and Novo Nordisk. Speaker Grants: AstraZeneca, Bioton, Boehringer-Ingelheim, Novo Nordisk, Mundipharma. K.S., Personal Fees: Sanofi, AstraZeneca, Novo Nordisk, MSD, Bayer, ICON. T.M., Research Grants: Sanofi, Novo Nordisk, TrialNet, Amarin.

Figures

FIG. 1.

HbA1c (% and mmol/mol) by study visit (A), FPG (mmol/L and mg/dL) by study visit (B), and seven-point SMPG profiles (mmol/L and mg/dL) at baseline and week 26 (C). Data are mean ± standard error. BL, baseline; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; SMPG, self-monitored plasma glucose; W, week.

FIG. 2.

Daily basal and mealtime insulin doses (U/kg) in patients with T1D (A) and T2D (B) (safety population). Data are mean ± standard error. BL, baseline; D, day; T1D, type 1 diabetes; T2D, type 2 diabetes; W, week.