The current global prevalence is approximately 160 million people and has been estimated to increase to 300 million people in 2025. Diabetes is currently the sixth leading cause of death by disease in the US and is estimated to cost the US health care system $100 billion (€84 billion) per year.
It is estimated that by the year 2010, diabetes will exceed both heart disease and cancer as the leading cause of death through complications.
The unmet need for new, safe and effective treatment tools to prevent the progression of the type 2 diabetes, its serious complications and the associated over-mortality in this disease remains enormous.
Under the terms of the expanded agreement, >Amgen will now receive exclusive worldwide rights to develop and commercialise Biovitrum's small molecule 11b-HSD1 enzyme inhibitors for the treatment of metabolic diseases and certain other medical disorders.
"Amgen has proven to be an excellent partner for our 11b-HSD1 enzyme inhibitor program and we are very happy to expand this collaboration," said Mats Pettersson, CEO of Biovitrum.
"We are confident that Amgen will remain a strong and committed partner for completing development of this innovative approach for helping those suffering from type 2 diabetes and related disorders," he added.
Excess glucocorticoids such as cortisol produce visceral obesity and diabetes. 11beta-hydroxysteroid dehydrogenases (11ß-HSDs) are enzymes that play an important role in the interconversion of glucocorticoids between the active and inactive forms.
Two enzymes have been identified, 11ß-HSD1, and 11ß-HSD2. These 11ß-HSDs play a major role in the modulation of local cortisol levels and the access of active steroid to its receptors in the target tissues.
Therefore, the 11ß-HSDs are also believed to have important roles in a number of common diseases, including obesity, type 2 diabetes and hypertension.
11ß-HSD2 is found primarily in tissues such as kidney, sweat glands and salivary glands. 11ß-HSD2 converts active glucocorticoids into inactive steroids and appears to act as an effective barrier to excess cortisol across a wide range of cortisol concentrations.
However, in studies where the 11ß-HSD2 enzyme activity has been inhibited with liquorice this results in an excess of steroids that cause hypokalemia and hypertension.
11ß-HSD1 is present in tissues of importance for metabolism and insulin sensitivity such as the liver and the adipose tissue. Its activity can be altered by factors such as glucocorticoids, stress, sex steroids, growth hormone, cytokines and PPAR agonists.
Under normal conditions, 11ß-HSD1 is believed to amplify local glucocorticoid concentrations in target tissues, in particular when the circulating plasma cortisol levels are low.
However, in obese subjects the levels of 11ß-HSD1 are usually markedly increased, at least in adipose tissue. This observation is of importance in the light of a rodent study recently published in Science, demonstrating that animals with an increased 11ß-HSD1 activity (i.e. transgenic animals) have an excess of visceral fat and are insulin resistant, diabetic and dyslipidemic.
Furthermore, in humans, pharmacological inhibition of 11ß-HSD1 with non-selective compounds has previously been shown to result in enhanced insulin sensitivity.
This finding indicates that 11ß-HSD1 appears to play an important role in type 2 diabetes and the metabolic syndrome also in man, and that selective inhibitors of 11ß-HSD1 could become a very useful tool in the treatment of this disorder.
The original development and marketing collaboration agreement, announced in September 2003, provides Amgen the exclusive right to commercialise products in North and South America, the European Union, Australia and New Zealand.
Under the expanded agreement, Amgen receives exclusive worldwide rights to commercialise all developed products, while Biovitrum retains co-promotion rights in the Nordic region for all products developed.
Amgen will pay an undisclosed amount for the upfront payment related to the expanded licensed territory.
Amgen will also fund and conduct all further development and commercialization activities worldwide. Biovitrum may receive additional milestone payments related to development progress and regulatory submissions for metabolic diseases.
Once a product has been approved, Biovitrum will receive tiered royalties on future worldwide sales of all products arising from the agreement.
Type 2 diabetes is a lifestyle disease with a strong hereditary component. Estimates of diabetes prevalence around the world have more than tripled since 1985.
Presently, approximately 6 percent of the population in the United States is diabetic. Of these patients, 90-95 percent are afflicted with different forms of type 2 diabetes, a condition that is expected to become increasingly widespread, due to the increasing number of elderly, a more sedentary lifestyle and rapidly growing incidence of obesity.
The worldwide annual average mortality in diabetics (5.4 per cent) is twice as high as in non-diabetics.
Each year in the United States alone type 2 diabetes results in about 200,000 deaths, 400,000 heart attacks, 130,000 strokes, 60,000 amputations, 10,000 new cases of kidney failure requiring dialysis or transplantation and 6,000 new cases of blindness.
Type 2 diabetes also leads to other disabilities, especially nerve damage, that could result in erectile dysfunction, numbness, intractable nausea, and diarrhoea.