Copenhagen, 2012-10-04 11:10 CEST (GLOBE NEWSWIRE) --
Press Release
No. 8/2012
- Data on ZP3022, a novel GLP-1-gastrin dual agonist, revealed by the company in presentations at the European Association for the Study of Diabetes 48th Annual Meeting -
Copenhagen, 4 October 2012 – Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL) reports that new data from preclinical studies with a novel peptide agonist, ZP3022, from the company’s GLP-1-gastrin dual agonist program, demonstrate a significant increase in pancreatic beta-cell mass associated with a significant improvement in glycemic control. The data were revealed by the company yesterday in a poster presentation at the European Association for the Study of Diabetes (EASD) 48th Annual Meeting in Berlin, Germany.
Christian Grøndahl, Chief Scientific Officer at Zealand Pharma, commented:
“We continue to see exciting results in our GLP-1-gastrin dual agonist program, representing a novel approach to the treatment of diabetes with potential disease modifying properties. The new data we present at EASD from studies in preclinical models of diabetes show that the GLP-1-gastrin dual acting peptide, ZP3022 significantly enhances beta-cell mass associated with a significant decrease in blood sugar. These findings further substantiate the therapeutic rationale for GLP-1-gastrin dual agonists as a potential future new treatment option for patients with Type 2 diabetes. With their potential to alter the chronic progression of the disease, there may also be a possible role for this type of compound in the treatment of Type 1 diabetes.”
The poster presentation is titled
“The Novel GLP-1-Gastrin Dual Agonist ZP3022 Improves Glycemic Control in ZDF Rats” (J. Skarbaliene et al, Zealand Pharma A/S)
Study design
In the study, 84 diabetic Zucker Diabetic Fatty (fa/fa) rats (11 weeks of age) were stratified into seven treatment groups of n=12 with matching HbA1c and blood glucose (BG) levels. 12 lean ZDF (fa/+) rats were used as lean controls.
The ZDF (fa/fa) rats were dosed subcutaneously twice daily (BID) for eight weeks with vehicle, ZP3022 (10, 40 nmol/kg), liraglutide (40 nmol/kg), exendin-4 (30 nmol/kg), gastrin17 (80 nmol/kg) or exendin-4 plus gastrin 17 (30 + 80 nmol/kg). Lean rats were dosed with vehicle.
HbA1c was measured at the start and end of treatment and an oral glucose tolerance test was performed after five weeks of treatment. Fed blood glucose was measured every other week and beta-and alpha-cell mass was determined at the end of the study.
Study conclusion
Treatment with ZP3022 significantly enhanced beta-cell mass (per BW) and improved glycemic control in diabetic Zucker Diabetic Fatty rats, as evidenced by a significant decrease in HbA1c levels and blood glucose concentrations as well as improvements in glucose tolerance and increased insulin levels after an oral glucose tolerance test. Notably, ZP3022 had a significantly better effect on beta-cell mass and glycemic control than liraglutide at equimolar dose. The anti-diabetic effects of ZP3022 make this compound a promising therapeutic candidate for the treatment of type 2 diabetes.
In an oral presentation today, Trine S. R. Neerup, Zealand Pharma, presented results from a study showing the anti-diabetic effects of ZP3022 in a diabetic mouse model under the following title:
“The GLP-1-Gastrin dual agonist ZP3022 increases beta cell mass via an increase in mean islet mass in db/db mice” (D Almholt et al, Zealand Pharma A/S)
The results and conclusions from this study was also presented at the American Diabetes Association’s Annual Scientific Sessions earlier this year and reported by Zealand Pharma in Press Release no. 03/2012 on 10 June 2012.
Study results and conclusion
In this 8 week study, treatment of diabetic db/db mice with ZP3022 caused a sustained increase in beta-cell mass accompanied by a significant improvement in glycemic control as measured by HbA1c. In comparison, liraglutide also caused improved glycemic control, but displayed only a transient effect on beta-cell mass.
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For further information, please contact:
Zealand Pharma A/S
David H. Solomon, President & CEO, Tel: +45 22 20 63 00
Hanne Leth Hillman, Vice President, Director of IR & Corporate Communication,
Tel: +45 50 60 36 89, email: hlh@zealandpharma.com
About Diabetes
Diabetes is a long-term disease that occurs either when the pancreas does not produce enough insulin (the hormone that regulates blood glucose concentrations), or when the body cannot effectively use the insulin it produces, or both. This results in raised blood glucose concentrations (hyperglycemia). Over time, uncontrolled hyperglycemia leads to the macrovascular and microvascular complications of diabetes. Macrovascular complications, which affect the large blood vessels, include heart attack, stroke and peripheral vascular disease. Microvascular complications affect the small blood vessels of the eyes (retinopathy), kidney (nephropathy) and nerves (neuropathy). The incidence of Type 2 diabetes is growing at an alarming rate. Over 310 million people worldwide is living with the condition today and the number is expected to increase to more than 550 million people in 2030.
About GLP-1 receptor agonists
GLP-1 (glucagon-like peptide-1) is a naturally occurring peptide hormone that is released from the intestinal L-cells within minutes of food ingestion. The main physiological actions of GLP-1 are glucose-dependent stimulation of insulin secretion from pancreatic beta-cells and suppression of glucagon secretion from pancreatic alpha-cell secretion of glucagon.
GLP-1 receptor agonists are members of an established class of diabetes drugs approved by regulatory authorities and marketed globally as mono andadd-on treatment for patients with Type 2 diabetes. Their use is endorsed by the European Association for the Study of Diabetes, the American Diabetes Association, the American Association of Clinical Endocrinologists and the American College of Endocrinology. Several novel GLP-1 receptor agonists are in development.
About gastrin
Gastrin is a naturally-occurring peptide hormone that is released primarily from G-cells in the stomach during meal ingestion. The main action of gastrin is to stimulate the secretion of gastric acid, a fluid that assists with the breakdown and digestion of food. Gastric acid works in conjunction with enzymes to process nutrients from food and create waste, which is sent to the intestines. It has also been suggested that gastrin plays a role in pancreatic development.
About GLP-1-gastrin dual agonists and ZP3022
ZP3022 is a compound from Zealand Pharma’s preclinical drug discovery program on dual acting GLP-1-gastrin peptide agonists, designed to act on both the GLP-1 and the gastrin receptors. In preclinical disease models of diabetes (db/db mice and Zucker Diabetic Fatty (ZDF) rats), ZP3022 has been shown to increase beta cell mass (insulin producing cell mass) to a greater extent than liraglutide. Moreover, ZP3022 has been shown to significantly improve glycemic control in diabetic mice both during treatment and in a follow up period after end of treatment.
About Zealand Pharma
Zealand Pharma A/S (NASDAQ OMX: ZEAL) is a biotechnology company based in Copenhagen, Denmark. Zealand Pharma specializes in the discovery, optimization and development of novel peptide drugs and has a broad and mature pipeline of drug candidates identified through its own drug discovery activities. The company’s lead drug invention is lixisenatide (Lyxumia®), a once-daily GLP-1 agonist, which is licensed to Sanofi for the treatment of Type 2 diabetes. In November 2011, Sanofi filed for registration of lixisenatide in Europe and regulatory filing in the United States is expected in December 2012.
Zealand Pharma has a partnering strategy for the development and commercialization of its products and in addition to the collaboration with Sanofi in Type 2 diabetes, the company has partnerships with Boehringer Ingelheim in diabetes/obesity, Abbott in acute kidney injury and Helsinn Healthcare in chemotherapy induced diarrhea. Zealand Pharma focuses its activities in disease areas where existing treatments fail to adequately serve patient needs and where the market potential for improved treatments through the use of peptide drugs is high.
