Development of Insulin Detemir/Insulin Aspart Cross-Reacting Antibodies Following Treatment with Insulin Detemir: 104-week Study in Children and Adolescents with Type 1 Diabetes Aged 2-16 Years.

Background: To study the long-term development (104 weeks) of insulin antibodies during treatment with insulin detemir (IDet) and insulin aspart (IAsp) in children with type 1 diabetes aged 2-16 years.

Methods: A 52-week, two-arm, randomized trial comparing IDet and neutral protamine Hagedorn insulin, both in combination with IAsp, was followed by a one-arm, 52-week extension trial of the IDet + IAsp arm. The present analysis was conducted in children who completed the randomized trial and entered into the extension trial.

A fit-for-purpose strategy for the risk-based immunogenicity testing of biotherapeutics: a European industry perspective.

There is much debate in the pharmaceutical industry on how to translate the current guidelines on immunogenicity testing for biotherapeutics into a testing strategy that suits the specific requirements of individual drug candidates. In this paper, member companies from the European immunogenicity platform (EIP) present a consensus view on the essential requirements for immunogenicity testing of a biotherapeutic throughout the various phases of drug development, to ensure patient safety and to enable successful market entry. Our aim is to open the debate and provoke discussion on this important topic which is unique to biotherapeutic drug development.

In vitro protein binding of liraglutide in human plasma determined by reiterated stepwise equilibrium dialysis.

Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue approved for the treatment of type 2 diabetes. It is based on human GLP-1 with the addition of a 16-carbon fatty acid, which facilitates binding to plasma proteins, thus prolonging the elimination half-life and allowing once-daily administration. It has not been possible to quantify liraglutide protein binding by ultrafiltration (the usual method of choice), as the lipophilic molecule becomes trapped in the filter membrane.

Immunogenicity of novel recombinant human activated factor VII analogues on factor VII neonatally-tolerized rats.

Recombinant activated factor VII (rFVIIa; NovoSeven) has been widely used to treat bleeding in patients with haemophilia with inhibitors. To increase the intrinsic activity, analogues of rFVIIa (rFVIIa Q, rFVIIa DVQ, and rFVIIa DVQA) with altered amino acid sequence at or near the active centre have been developed. The immunogenicity of these analogues was tested in a rat immune tolerance model.