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 Ò / NovoRapid Ò (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 Ò ), 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 selfmonitored 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.

Efficacy, Safety, and Immunogenicity of Insulin Aspart Biosimilar SAR341402 Compared with Originator Insulin Aspart in Adults with Diabetes (GEMELLI 1): A Subgroup Analysis by Prior Type of Mealtime Insulin

“…In GEMELLI 1, adults with T1D or T2D were pre-treated with commercial mealtime NN-Asp or insulin lispro (Humalog ® /Liprolog® 100 U/mL; Eli-Lilly, Indianapolis, IN, USA) [ 9 – 11 ] therapy. Results for the overall study population following 6- and 12-months treatment have been previously reported [ 6 , 7 ] and confirm that SAR-Asp and NN-Asp have similar efficacy, safety, and immunogenicity profiles.…”

“…The study comprised a 2-week screening period, a 6-month (26-week) efficacy and safety period, and a 6-month (26-week) safety extension period (for an overall 52-week period). The study design, participants, and methods of the trial, performed according to ethical principles described in the International Conference on Harmonisation Guidelines for Good Clinical Practice and the Declaration of Helsinki, have been previously reported [ 6 , 7 ]. The protocol was approved by an independent ethics committee or institutional review board for each center; written informed consent was obtained from each patient before any trial-related activities.…”

“…At randomization, participants received a SAR-Asp or NN-Asp starting dose that was a unit-to-unit (1:1) conversion from the NovoLog/NovoRapid or Humalog/Liprolog dose used prior to the trial or a dose at the discretion of the investigator, taking into account the glucose control at the time of randomization. Mealtime insulin and Gla-100 doses were then titrated to achieve protocol‐specified glycemic targets [ 6 , 7 ].…”

“…For other study visits, insulin dose values were reported as the median of daily doses available in the week prior to the study visit. Details on efficacy, safety, and immunogenicity outcomes have been previously reported [ 6 , 7 ].…”

“…The HbA1c analyses were performed using the intent-to-treat population, which included all randomized participants irrespective of compliance with the study protocol and procedures [ 6 , 7 ]. Insulin dose, hypoglycemia, and adverse event analyses used the safety population, comprising all randomized participants who received at least one dose of study insulin, analyzed according to the treatment actually received.…”