STOCKHOLM, Sweden, March 11, 2002 (PRIMEZONE) -- Biovitrum today announced that it has entered Phase I studies with BVT.3498, a selective 11B HSD-1 inhibitor for the treatment of Type II diabetes.
In addition to demonstrating improved insulin sensitivity and glycemic control, the development program will be designed to establish positive effects on body composition, lipid profile and other metabolic aberrations linked to insulin resistance, either as monotherapy or as add-on treatment to other therapies.
"BVT.3498 has the potential to become the therapy of choice for type II diabetes, especially with the additional positive effects that we expect it will bring to overweight and obese patients with type II diabetes," said Johan Kordel, Head of Research at Biovitrum.
Biovitrum is a private Swedish biopharmaceutical company active within research and development of small molecule therapeutics and recombinant proteins. The research is focused on metabolic disorders, such as diabetes and obesity. Recently, Biovitrum announced that the company has achieved positive proof of concept data in man for their first anti- obesity agent BVT.933, a 5HT2c agonist. Biovitrum also covers other selected therapeutic areas. ReFacto (a recombinant factor VIII treatment for hemophilia), acquired by American Home Products provides the company with substantial revenues from royalty, co-promotion and supply arrangements. A separate division of the company develops, produces and markets human-derived plasma products.
Note to Editors:
Biovitrum is a private Swedish biopharmaceutical company active within research and development of small molecule therapeutics and recombinant proteins. The research is focused on metabolic disorders, such as diabetes and obesity, but also covers other selected therapeutic areas. ReFacto (a recombinant factor VIII treatment for hemophilia), acquired by American Home Products, provides the company with substantial revenues from royalty, co-promotion and supply arrangements. A separate division of the company develops, produces and markets human-derived plasma products.
11B-HSD
Excess glucocorticoids produce visceral obesity and diabetes. 11B- hydroxysteroid dehydrogenases (11BHSDs) are enzymes that play an important role in the interconversion of active glucocorticoids between its active and inactive forms. Two enzymes have been identified, 11BHSD- 1, and 11BHSD-2. These 11BHSDs play a major role in the modulation of local cortisol levels and the access of active steroid to its receptors in the target tissues. Thereby, the 11BHSDs are also believed to have important roles in a number of common diseases, including obesity, type II diabetes and hypertension.
11BHSD-2 is found primarily in tissues such as kidney, sweat glands and salivary glands. 11BHSD-2 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 11BHSD-2 enzyme activity has been inhibited with liquorice this results in an excess of steroids that cause hypokalemia and hypertension.
11B HSD-1 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, 11B HSD-1 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 11B HSD-1 are usually markedly increased, at least in adipose tissue. This observation is of importance in the light of a recently published rodent study in Science, demonstrating that animals with an increased 11B HSD-1 activity (i.e., transgenic animals) have an excess of visceral fat and are insulin resistant, diabetic and dyslipidemic. Furthermore, in humans, pharmacological inhibition of 11B HSD-1 with non-selective compounds, has previously been shown to result in enhanced insulin sensitivity. This finding indicates that 11B HSD-1 appears to play an important role in type II diabetes and the metabolic syndrome also in man, and that selective inhibitors 11B HSD-1 could become a very useful tool in the treatment of this disorder.
Type II Diabetes (also known as non-insulin dependent, adult onset or type II diabetes mellitus)
Type II diabetes is a lifestyle disease with a strong hereditary component. Estimates of diabetes prevalence around the world have more than tripled since 1985. The current global prevalence is approximately 160 million people and has been estimated to increase to 300 million people in 2025. Presently, approximately 6% of the population in the United States is diabetic. Of these patients, 90-95% are afflicted with different forms of type II 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%) is twice as high as in non-diabetics. Each year in the United States alone, 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 result from type II diabetes. Type II diabetes also leads to other disabilities, especially nerve damage that could result in erectile dysfunction, numbness, intractable nausea, and diarrhea. Diabetes is currently the sixth leading cause of death by disease in the United States and is estimated to cost the US health care system 100 billion USD 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.
Type II diabetes is a progressive disease caused by a combination of decreased tissue sensitivity to insulin (insulin resistance) and an insufficient insulin secretion. The blood glucose control in type II diabetes usually deteriorates over time and, despite lifestyle intervention efforts, additional pharmacological treatment in many cases ultimately becomes necessary. Type II diabetes is frequently associated with obesity, dyslipidemia, hypertension, atherosclerosis, thrombosis and cardiovascular disease. In the treatment of diabetes it is important to address all these aspects of the disease. The unmet need for new, safe and effective treatment tools to prevent the progression of the type II diabetes, its serious complications and the associated over- mortality in this disease remains enormous.
Phase I clinical trials establish tolerability of a drug candidate, and are usually performed in healthy volunteers.
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