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

Abstract

Background: SAR341402 (SAR-Asp) is a biosimilar/follow-on of the originator insulin aspart-NovoLog®/NovoRapid® (NN-Asp). This study investigated whether the efficacy, safety, and immunogenicity findings for SAR-Asp versus NN-Asp, observed over 6 months in people with type 1 (n = 497) or type 2 diabetes (n = 100) treated with multiple daily injections in combination with insulin glargine (Lantus®), are maintained after 12 months. Materials and Methods: GEMELLI 1 was a multicenter, randomized, open-label, phase 3 study. Participants completing the initial 6-month treatment period continued on SAR-Asp or NN-Asp, as randomized, for a 6-month safety extension. Results: Of the 597 participants randomized, 264 out of 301 (87.7%) and 263 out of 296 (88.9%) assigned to SAR-Asp and NN-Asp, respectively, completed 12 months of treatment. Improved glycemic control was sustained at 12 months in both treatment groups, with similar least-squares mean reductions in glycated hemoglobin (HbA1c) from baseline (SAR-Asp: -0.25%; NN-Asp: -0.26%). Fasting plasma glucose and seven-point self-monitored plasma glucose profile changes, including postprandial glucose excursions, and changes in mealtime and basal insulin dosages were similar between groups. Safety and tolerability, including anti-insulin aspart antibodies (AIAs; incidence, prevalence, titers, cross-reactivity to human insulin), neutralizing antibodies (incidence, prevalence), hypoglycemia, and treatment-emergent adverse events (including hypersensitivity events and injection site reactions), were similar between groups. No relationship was observed between maximum individual AIA titers and change in HbA1c or insulin dose, hypoglycemia, or hypersensitivity reactions or between efficacy/safety measures and subgroups by presence or absence of treatment-emergent AIA. Conclusions: SAR-Asp and NN-Asp demonstrated similar efficacy and safety (including immunogenicity) in people with diabetes over 12 months of treatment.

Keywords: Biosimilar; Follow-on product; 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., P.M., and B.M. are all employees and stockholders of Sanofi. F.D., employee of Ividata. 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. V.N.S., V.N.S.’ 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., Novo Nordisk, 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.

Figures

FIG. 1.

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

FIG. 2.

HbA1c (% and mmol/mol) by study visit (A), least-squares mean change in HbA1c from baseline to week 26 and 52 (B), FPG (mmol/L and mg/dL) by study visit (C), and seven-point SMPG profiles (mmol/L and mg/dL) at baseline and week 52 (D). Data are mean ± SE. FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; SMPG, self-monitored plasma glucose.

FIG. 3.

Boxplots of AIA titer (1/dilution) at each study visit during the 12-month on-treatment period (AIA population). At each visit, AIA titers are described for participants with a positive-sample AIA status at the visit. The boxplot provides the 25% (Q1), 50% (median), and 75% (Q3) quartiles (lower, middle, and upper horizontal bars of the box, respectively). The diamond represents the mean, and triangles or squares represent values beyond the upper/lower whiskers (defined as 1.5 times the interquartile range). Each symbol for high/low values could represent more than one participant. AIA, anti-insulin aspart antibody; Q, quartile.