SAR341402 (SAR-Asp), NovoLog (NN-Asp-US) and NovoRapid (NN-Asp-EU) are rapid-acting insulin aspart products.
Exposure (PK) to and activity (PD) of SAR-Asp (T) NN-Asp-US (R1) and NN-Asp-EU (R2) were compared in a single-center, randomized, double-blind, 3-treatment, 3-period, crossover, euglycemic clamp study. Thirty male T1D subjects (22-59 years) were randomized to receive 0.3 U/kg T, R1 and R2 in separate periods; 29 subjects completed all 3 treatment periods. PK and PD (Glucose Infusion Rate, GIR) by euglycemic clamp were assessed up to 12 hours.
Mean concentration and body weight standardized GIR vs. time profiles for T, R1 and R2 were similar. Exposure to and activity of T, R1 and R2 were similar between treatments, as the 90% CIs for the treatment ratios for the primary and main secondary PK and PD endpoints were within the predefined acceptance range (0.80-1.25) (Table). Within-subject variability of exposure and activity was low across the 3 clamps, indicating high day-to-day reproducibility in clamp performance, irrespective of the individual product. Adverse events were similar for T, R1 and R2. No safety concerns were noted in laboratory, vital signs, or ECG data.
In summary, this study demonstrated similar insulin aspart exposure profiles and PD activity for SAR-Asp to NN-Asp-US and NN-Asp-EU and between NN-Asp-US and NN-Asp-EU, rendering SAR-Asp a biosimilar/follow-on product.
C. Kapitza: Research Support; Self; ADOCIA, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Mylan, Nestlé, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi-Aventis, Wockhardt, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. L. Nosek: None. A. Lehmann: Employee; Self; Sanofi-Aventis Deutschland GmbH. W. Schmider: Employee; Self; Sanofi. B. Rotthaeuser: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. I.K. Nowotny: Employee; Self; Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Self; Sanofi.