Visual Abstract

This randomized, double-blind, three-way crossover trial (NCT04235439) compared the PK and PD properties of GL-LIS, a proposed biosimilar LIS by Gan & Lee, US- and EU-licensed Humalog® (US-LIS and EU-LIS) in 38 healthy male subjects (mean±SD age 41±15 years, BMI 24.4±2.8 kg/m²). Each subject received a single 0.2 U/kg dose of either GL-LIS, US-LIS or EU-LIS in each of the 3 euglycemic glucose clamp periods (ClampArt, clamp level 81 mg/dl, clamp duration 12h post-dose). GL-LIS and comparator insulins showed superimposable serum LIS concentration- and glucose infusion rate (GIR) profiles (Figure). PK BE was demonstrated between GL-LIS and the two comparator insulins as serum LIS concentration point estimates (using log-transformed data) were close to 100% and the 90% CIs were well contained within the pre-defined similarity margins of 80-125% (Figure). Likewise, the primary PD endpoints met BE-criteria as did multiple secondary PK/PD-endpoints, including AUCLIS.0-2h, AUCLIS.0-4h, AUCLIS.0-6h, AUCGIR.0-2h, AUCGIR.0-4h, AUCGIR.0-6h, and AUCGIR.6-12h. Several sensitivity analyses confirmed BE. All insulins had a low incidence of adverse events (5-11 events per insulin). No injection site reactions were observed.

In conclusion, GL-LIS demonstrated both PK- and PD-bioequivalence to US- and EU-licensed LIS formulations.

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Disclosure

E. Zijlstra: Speaker’s Bureau; Self; Novo Nordisk A/S. T. Heise: Advisory Panel; Self; Novo Nordisk A/S, Valbiotis, Research Support; Self; ADOCIA, Afon Technology Ltd., AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, Julphar, Mylan N. V., Nestlé, Neuraly, Nordic Bioscience, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker’s Bureau; Self; Novo Nordisk A/S. M. Ermer: None. J. Lu: Employee; Self; Gan & Lee Pharmaceuticals. M. G. Wilson: Consultant; Self; Gan & Lee Pharmaceuticals, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. L. Plum-moerschel: None.

Funding

Gan & Lee Pharmaceuticals

© 2021 by the American Diabetes Association
2021
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