The first biosimilar of ultra-rapid insulin lispro: results of a double-blind randomised clamp study

Abstract

Introduction. Over the years, insulin therapy has remained an important component of the complex treatment of patients with diabetes mellitus. Ultra-rapid insulin lispro is a DNA recombinant analogue of human insulin, which has a pharmacokinetic (PK) profile that is as close as possible to the endogenous insulin secretion profile, which ensures effective control of postprandial glycaemia. The development of the ultra-rapid insulin lispro biosimilar will expand the range and increase the availability of modern and safe insulin analogues for diabetic patients in Russia.Aim. To compare the PK and pharmacodynamic (PD) profiles of GP40261 (ultra-rapid insulin lispro biosimilar) and the reference Lyumjev® in healthy volunteers.Materials and methods. This was a double-blind, randomised, comparative, crossover study in healthy volunteers who were administered either the test or reference ultra-rapid insulin lispro formulation as a single dose of 0.3 IU/kg. The hyperinsulinaemic euglycaemic clamp technique was used to evaluate the pharmacokinetics and pharmacodynamics of the study products. In order to assess the biosimilarity of the products, 90% confidence intervals (CIs) were calculated for geometric mean ratios of the primary PK parameters AUCins.0-t and Cins.max. The PD parameters of the study drugs were evaluated based on the glucose infusion rate required to maintain the target glycaemic level during the clamp.Results. The 90% CIs for the geometric mean ratios of the primary PK parameters for the test and reference products were 89.41-94.55% for AUCins.0-t and 82.74-92.92% for Cins.max, which complies with the established acceptance limits of 80-125% for both parameters. The study products were also found to have comparable PD profiles of their active substances.Conclusion. This clinical study has demonstrated that GP40261 and the reference ultra-rapid insulin lispro are biosimilar and have a comparable safety profile.