Oral Delivery Of GLP-1 And PYY

Results showed that Emisphere’s eligen(R) technology can orally deliver the incretin hormones GLP-1 and PYY. The oral administration of both peptides induced a rapid and dose-dependent, statistically significant increase in plasma drug concentrations at all doses tested versus placebo. Emisphere Technologies, Inc. (Nasdaq: EMIS) reported results of two clinical studies conducted in collaboration with Professor Christoph Beglinger, M.D. Division of Gastroenterology and Hepatology, University Hospital Basel in Basel, Switzerland. The objective of the study with glucagon-like peptide-1 (7-36 amide) (GLP-1) was to establish the initial pharmacological profile and the insulin releasing activity of increasing oral doses of GLP-1 in healthy volunteers. In addition, the pharmacokinetic effects of GLP-1 were investigated after intravenous administration. The objective of the study with peptide YY 3-36 (PYY) was to establish the PYY plasma concentrations following increasing oral doses of the peptide.

The results showed that Emisphere’s eligen(R) technology can orally deliver the incretin hormones GLP-1 and PYY. The oral administration of both peptides induced a rapid and dose-dependent, statistically significant increase in plasma drug concentrations (p<0.05) at all doses tested versus placebo. Additionally, the orally delivered GLP-1 induced a statistically significant effect on insulin release in all healthy male volunteers (p<0.05) at all doses tested versus placebo. The Company expects these results to be published in a leading peer-reviewed scientific journal later this year.

GLP-1 was given orally to six healthy male subjects in a six way cross-over design. The treatment arms consisted of oral doses of GLP-1 (0.5, 1.0, 2.0 and 4.0 mg of drug) with Emisphere’s delivery agent administered as a single tablet versus placebo. Only one dose was given per day. On a separate day, subjects received an intravenous infusion of GLP-1 (0.4 pMol/kg/min infused for 45 minutes). Blood samples were obtained for GLP-1 and insulin concentrations.

In the PYY study, the drug was given orally to six healthy male subjects in a six way cross-over design. The treatment arms consisted of oral doses (0.25, 0.5, 1.0, 2.0 and 4.0 mg) of PYY with Emisphere’s delivery agent administered as a single tablet versus placebo. In addition, there was a reduction of Ghrelin in all groups administered PYY with the largest percent reduction in Ghrelin levels observed in the 4 mg PYY dose.

"This study showed for the first time that GLP-1 was active with regard to stimulation of insulin releases in humans after oral administration. In the subjects receiving the highest doses of oral GLP-1, we observed nausea effects similar to those seen when the subjects received high levels of injectable GLP-1. The biodynamic results on insulin release and blood concentrations indicate that oral GLP-1 could be an effective treatment in diabetes. The PYY results in combination with the GLP results could mean that oral PYY and oral GLP-1 could also be an effective treatment for other diseases such as obesity.

"We are very pleased to be working on the oral delivery of GLP-1 and PYY with a leading academic researcher such as Dr. Beglinger in the field of gastroenterology. The compounds GLP-1 and PYY are gastrointestinally produced hormones and GLP-1 is already an important compound in the treatment of diabetes as an injectable agent. Non-oral forms of these compounds are being explored in the treatment of obesity. We are looking forward in 2007 to initiating and completing a proof-of-concept efficacy study on the reduction of food intake using our oral incretin products with Dr. Beglinger," said Lewis H. Bender, President and CEO of Emisphere Technologies, Inc.

About GLP-1

Glucagon-like peptide-1 is synthesized in intestinal endocrine cells in two principal major molecular forms, as GLP-1(7-36) amide and GLP-1(7-37). The peptide was first identified following the cloning of cDNAs and genes for proglucagon in the early 1980s. The main target of action of glucagon-like peptide-1 (GLP-1) is the islet, where the hormone stimulates insulin secretion, promotes beta cell proliferation and neogenesis, and inhibits glucagon secretion. However, GLP-1 receptors are also expressed outside the islets, increasing the likelihood that GLP-1 also plays a role in other organs. These functions are mainly the inhibition of gastric emptying, gastric acid secretion and exocrine pancreatic secretion, indicating that the hormone acts as an enterogastrone — a hormone released from the distal portion of the small intestine that inhibits proximal gastrointestinal events. Another important action of GLP-1 is to induce satiety.

About PYY

Peptide YY 3-36 is produced by the gut and is released into the circulation in response to food ingestion. Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY 3-36, a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. It is believed that PYY may be an important regulator of food intake.

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