New Drug Approvals 2014 - Pt. X - Albiglutide (Eperzan™ or Tanzeum™)
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Wikipedia: Albiglutide
ChEMBL: CHEMBL2107841
Type II diabetes
Type II diabetes is a metabolic disorder that is characterized by high blood sugar (hyperglycemia) due to insulin resistance or relative lack of insulin. The disease affects millions of patient world-wide and can lead to long-term complications if the blood levels are not lowered in the patients: heart diseases, strokes and kidney failure.Albiglutide
The drug is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin.
Schematic representation of the albiglutide (EMA)
Mode of action
Traditionally, a decrease in the glucose blood level of affected patients is triggered using insulin injections. One alternative mechanism consists at indirectly stimulating insulin release using a glucagon-like peptide-1 (GLP-1) or an analogue of the corresponding receptor.
GLP-1 receptor agonists are of particular interest, as they naturally stop simulating insulin release when plasma glucose concentration is in the fasting range, and hence preventing hypoglycemia in the patient too.
The natural half-life of GLP-1 is less than 2 minutes in the human blood, the peptide is rapidly degraded by an enzyme called dipeptidyl peptidase-4. On the other hand, albiglutide half-life ranges between four to seven days (resistance to dipeptidyl peptidase-4), a considerably longer time than endogenous peptide and than the others GLP-1 analogous drugs (exenatide and liraglutide). This property allows to reduce the number of injections in diabetic patient to biweekly or weekly instead of daily, hence considerably increasing treatment overheads.
GLP-1 receptor agonists are of particular interest, as they naturally stop simulating insulin release when plasma glucose concentration is in the fasting range, and hence preventing hypoglycemia in the patient too.
The natural half-life of GLP-1 is less than 2 minutes in the human blood, the peptide is rapidly degraded by an enzyme called dipeptidyl peptidase-4. On the other hand, albiglutide half-life ranges between four to seven days (resistance to dipeptidyl peptidase-4), a considerably longer time than endogenous peptide and than the others GLP-1 analogous drugs (exenatide and liraglutide). This property allows to reduce the number of injections in diabetic patient to biweekly or weekly instead of daily, hence considerably increasing treatment overheads.
Clinical trials
A series of eight clinical trials involving over 2,000 patients with type II diabetes demonstrated the safety and effectiveness of the drug. Patients reported improved HbA1c level (hemoglobin A1c or glycosylated hemoglobin, a measure of blood sugar control). The most common side-effects observed were diarrhea, nausea, and injection site reactions.Indication and warnings
Albiglutide can be used as a stand-alone as well as in combination therapy (with metformin, glimepiride, pioglitazone, or insulin for instance). The drug is not suited to treat type I diabetes and not indicated for patients with increased ketones in their blood or urine. Albiglutide should be used only when diet and exercise therapies are not successful.The drug has an FDA boxed warning, as cases of tumors of the thyroid gland have been observed in rodent studies with some other GLP-1 receptor agonists. The FDA further required post-marketing studies regarding dose, efficacy and safety in pediatric patients and for cardiovascular outcomes in patients with high baseline risk of cardiovascular disease.
Tradenames
The drug was invented by Human Genome Sciences and was developed in collaboration with GSK. Albiglutide is marketed as Eperzan in Europe and Tanzeum in the USA.