Novo Nordisk has said that its candidate drug for type 2 diabetes – liraglutide – has been shown to both control blood glucose and help patent lose weight in a Phase IIb trial.
The Danish drugmaker said it will start a Phase III trial programme of the drug, an albumin-bound analogue of a human hormone known as glucagon-like peptide-1, in February 2006 Liraglutide was formerly known by the code name NN2211.
In the Phase IIb study, liraglutide was able to improve glycated haemoglobin (haemoglobin A1c) levels – a marker of blood glucose control – by 1.5% to 2% compared to placebo after 14 weeks’ treatment. Moreover, 45% of patients treated with liraglutide at the highest dose achieved a target HbA1c level of 7% or less: this was achieved by only 8% of the placebo group. An HbA1c level of 7% or less is the therapeutic target laid down by American Diabetes Association therapy guidelines.
In addition, patients treated with liraglutide reduced their bodyweight by approximately 3kg from a baseline average of around 90kg, according to Novo Nordisk. This is significant as most drugs to treat type 2 diabetes cause weight gain.
Liraglutide is a fully-human analogue of GLP-1, an incretin hormone that acts throughout the body to help maintain healthy blood sugar levels and to control appetite. In healthy individuals, GLP-1 levels rise during a meal and along with glucose stimulate the production of insulin. This response is blunted in type 2 diabetics. GLP-1 also contributes to the health and survival of the insulin-producing cells in the body .
The primary obstacle to the use of GLP-1 as a therapeutic for diabetes is its extremely short half-life of about five minutes in the body. Liraglutide offers once-daily dosing via an injection.
A number of other companies are developing drugs that mimic the effect of this hormone, notably Eli Lilly and Amylin, whose Byetta (exenatide) was launched for second-line use in type 2 diabetics in the USA in June. Sales kicked off at $18 million for the third quarter of 2005. Byetta is given twice-daily, although Lilly and Amylin recently reported promising data with a once-weekly formulation.
GlaxoSmithKline licensed rights to a GLP-1/albumin conjugate product from Human Genome Sciences a year ago. This compound, originally dubbed Albugon but now known as GSK716155, is in late-stage preclinical development. A similar product from Canadian company ConjuChem called DAC:GLP-1 is in Phase I testing but other trials have been out on hold following animal toxicity data on a diluent (D23) used in the product.
Meanwhile, Merck & Co and Novartis are developing another class of diabetes medications, the DPP-4 inhibitors, that boost and extend the action of incretin hormones. Merck presented Phase II data on its sitagliptin in September, and it is currently in Phase III testing, as is Novartis’ vildagliptin.