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.

Garg, Satish K; Wernicke-Panten, Karin; Wardecki, Marek; Kramer, Daniel; Delalande, Francois; Franek, Edward; Sadeharju, Karita; Monchamp, Travis; Miossec, Patrick; Mukherjee, Bhaswati; Shah, Viral N

BACKGROUND SAR341402 (SAR-Asp) is a biosimilar/follow-on of the originator insulin aspart-NovoLog®/NovoRapid® (NN-Asp). This study investigated if the efficacy, safety, and immunogenicity findings for SAR-Asp versus NN-Asp, observed over 6 months in people with type 1 (T1D, n=497) or type 2 diabetes (T2D, 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 597 participants randomized, 264/301 (87.7%) and 263/296 (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 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 (AIA; incidence, prevalence, titers, cross-reactivity to human insulin), neutralizing antibodies (incidence, prevalence), hypoglycemia, 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 treatment.