New Zealand Research May Re-define Management of Heart Failure in Diabetes

AUCKLAND , New Zealand , April 28/PRNewswire/ --    

Control of oxidised copper levels in the body may be as important as lowering blood glucose levels in preventing cardiovascular complications in diabetes mellitus, according to New Zealand researchers.

A study (1) published in the international journal Diabetes shows that abnormal levels of oxidised copper accumulate in the bodies of people with type 2 diabetes mellitus and provides further support for the idea that treatment with drugs that eliminate this form of copper may reduce the incidence of heart disease. Trientine, developed by New Zealand biotechnology company, Protemix, as Laszarin(TM) extracts oxidised copper, which is then excreted in the patient's urine.

The research led by Professor Garth Cooper at the University of Auckland could help to redefine the management of type 2 diabetes worldwide. Professor Cooper explained: "The research is significant in pointing to a new direction for the management of heart failure and other cardiovascular complications in diabetes. Heart disease is the leading cause of death in people with diabetes. Those at risk tend to have high tissue levels of oxidised copper, [copper (II)], and by attending to this copper imbalance we believe the outcome is likely to improve. It is a fundamental change in our understanding of the disease process and its therapy. In addition to glucose-lowering agents, most people with type 2 diabetes might also benefit from copper regulation therapy. We may be able to turn back the heart disease and the wider vascular complications."

Mark Yeager, Professor in the Departments of Cell Biology and Molecular Biology at The Scripps Research Institute and Director of Cardiovascular Research at the Scripps Clinic, La Jolla , CA , USA commented: "This could have a tremendous impact on the treatment of diabetic heart disease and address an unmet clinical need. In addition to glucose regulation, it is becoming standard practice for patients diagnosed with diabetes mellitus to be treated with statin drugs to prevent coronary artery disease. However, it is a paradigm shift to address metal imbalance as a strategy to treat heart muscle disease in diabetes."

Kenneth Reid, Professor of Immunochemistry, the University of Oxford , added: "Last year Professor Cooper's team announced that trientine appears to reverse heart disease in people suffering from diabetes and may lead to a more effective intervention in a major cause of death worldwide. These clinical trials should be watched carefully by clinicians. The work to date clearly shows that it is beneficial."

Diabetes is often accompanied by heart enlargement, heart dysfunction and coronary heart disease and these are major causes of death (2). According to the World Health Organisation over 180 million people have type 2 diabetes. Previous work by the Auckland researchers (2) showed that six month's treatment with trientine brought about a 25 per cent return to normal heart size people with diabetes that had enlarged hearts.

The new research showed that regulation of copper metabolism was abnormal in test subjects with diabetes and that Laszarin(TM) treatment increased elimination of oxidised copper. If successful in phase III trials, Laszarin(TM) has a potential worldwide market of over three million people with diabetic heart failure.

(1) G.J.S. Cooper, Y.-K. Chan, A.M. Dissanayake, F.E. Leahy, G.F. Keogh, C.M. Frampton, G.D. Gamble, D.H. Brunton, J.R. Baker, and S.D. Poppitt:   Demonstration of a Hyperglycemia-Driven Pathogenic Abnormality of Copper Homeostasis in Diabetes and Its Reversibility by Selective Chelation:   Quantitative Comparisons Between the Biology of Copper and Eight Other    Nutritionally Essential Elements in Normal and Diabetic Individuals.    Diabetes 54: (5) 2005

(2) G.J.S. Cooper and associates: Regeneration of the Heart in Diabetes  by Selective Copper Chelation. Diabetes 53:2501-2508, 2004

Notes:

a) Trientine (Laszarin(TM)) is an orally-active small molecule that selectively chelates the oxidised form of copper, which has been used in the treatment of the rare genetic disorder Wilson's disease for over 20 years.

b) Protemix is a US-New Zealand-based biopharmaceutical company established over ten years ago, with its global operations directed from offices in San Diego and research facilities located within The University of Auckland . It discovers and develops novel therapies for cardiovascular disease, diabetes mellitus and other metabolic disorders.

Further information:
Garth Cooper    Protemix Corporatio     Ph: +64-9-303-5351
Larry Ellingson     Protemix Corporation   Ph: +1-480-816-6411

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Lilly and Amylin Announce FDA Approval of Exenatide

INDIANAPOLIS and SAN DIEGO , April 29/PRNewswire/ --

- A New First-in-Class Treatment for Patients in the US with Type 2 Diabetes

The United States Food and Drug Administration (FDA) has approved exenatide as adjunctive therapy to improve blood sugar control in patients with type 2 diabetes who have not achieved adequate control on metformin and/or a sulfonylurea, two common oral diabetes medications. Exenatide is the first in a new class of medicines known as incretin mimetics. Exenatide will be available to pharmacies in the United States by June 1, 2005 .

The U.S. is the first country in the world to receive regulatory approval for exenatide. Lilly and Amylin anticipate submissions for regulatory review in other countries in the near future.

In clinical trials, exenatide has been shown to improve blood sugar control by lowering both postmeal and fasting glucose levels, leading to better long-term control as measured by hemoglobin A1C. Exenatide has been shown to do this through several actions, including the stimulation of insulin secretion only when blood sugar is high and by restoring the first-phase insulin response, an activity of the insulin-producing cells in the pancreas that is lost in patients who have type 2 diabetes. Most patients in the long-term exenatide clinical studies required for registration in the U.S. also experienced reductions in weight.

Prof. Anthony Barnett, professor of medicine and honorary consultant physician at the University of Birmingham, United Kingdom said. "A treatment that lowers blood sugar, lowers weight and has the potential to help restore the response of the body's insulin-producing cells could be a unique and important contribution to the treatment of type 2 diabetes in Europe in the future."

In addition to approving exenatide for use as an adjunct to existing oral medicines, the FDA also stated that exenatide is approvable as a stand-alone therapy (monotherapy) for patients with type 2 diabetes. Any additional data submitted to support a monotherapy indication is expected to receive a six-month review.

Exenatide is formulated for self-administration as a fixed dose, subcutaneous injection given prior to the morning and evening meals.   Exenatide will be made available in the United States in both a 5-microgram per dose and a 10-microgram per dose prefilled pen-injector device.

About exenatide

Exenatide is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics and exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the stomach, liver, pancreas and brain that work in concert to regulate blood sugar.(1) Exenatide was approved by the FDA for use by people with type 2 diabetes who are unsuccessful at controlling their blood sugar levels despite using the commonly prescribed oral medications metformin, a sulfonylurea or both. The U.S. is the first country in the world to receive regulatory approval for exenatide. Lilly and Amylin anticipate submissions for regulatory review in other countries in the future.

About Incretin Mimetics

Incretin mimetics represent a new class of therapeutics for use in the fight against type 2 diabetes. An incretin mimetic works to mimic the antidiabetic or glucose-lowering actions of naturally occurring human hormones called incretins. These actions include stimulating the body's ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake. Exenatide is the first FDA-approved agent of this new class of medications.

(3/5/05)