- Study shows orally-delivered GLP-1 is able to stimulate insulin release
- Results to be published in peer-reviewed journal
- Proof of concept efficacy study on reduction of food intake planned for
2007
TARRYTOWN, N.Y., March 29 /PRNewswire-FirstCall/ -- Emisphere
Technologies, Inc. (Nasdaq: EMIS) reported today 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. The Cmax plasma concentration for the 4
mg oral dose of GLP-1 was 300 pMol/L.
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. The Cmax
value of PYY for the 4 mg oral dose had a plasma concentration of 629
pg/ml. 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 will seek to publish these results," said Dr.
Christoph Beglinger of the University Hospital in Basel.
"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.
About Diabetes
According to statistics provided by the World Health Organization and
the American Diabetes Association, approximately 177 million people
worldwide are afflicted by diabetes, with approximately 18 million of those
afflicted residing in the United States. Nearly one-third of all
individuals in the United States suffering from diabetes are unaware that
they have this chronic disease. Type 2 diabetics account for approximately
90-95% of diabetes cases. According to the publicly filed annual reports of
leading insulin manufacturers, worldwide sales of insulin were
approximately $5.6 billion in 2004. Currently, there are no approved
insulin therapies in oral form.
About Obesity
Obesity is a complex, multi-factorial chronic disease involving
environmental (social and cultural), genetic, physiologic, metabolic,
behavioral and psychological components. It is the second leading cause of
preventable death in the U.S. According to the American Obesity Association
approximately 127 million adults in the U.S. are overweight, 60 million
obese, and 9 million severely obese. Body Mass Index (BMI) is a measurement
tool used to determine excess body weight. Overweight is defined as a BMI
of 25 or more, obesity is 30 or more, and severe obesity is 40 or more.
Obesity increases the risk of illness from about 30 serious medical
conditions. Overweight or obese individuals experience social
stigmatization and discrimination in employment and academic situations.
About Emisphere Technologies, Inc.
Emisphere Technologies, Inc. is a biopharmaceutical company pioneering
the oral delivery of otherwise injectable drugs. Emisphere's business
strategy is to develop oral forms of injectable drugs, either alone or with
corporate partners, by applying its proprietary eligen(R) technology to
those drugs or licensing its eligen(R) technology to partners who typically
apply it directly to their marketed drugs. Emisphere's eligen(R) technology
has enabled the oral delivery of proteins, peptides, macromolecules and
charged organics. Emisphere and its partners have advanced oral
formulations or prototypes of salmon calcitonin, heparin, insulin,
parathyroid hormone, human growth hormone and cromolyn sodium into clinical
trials. Emisphere has strategic alliances with world-leading pharmaceutical
companies. For further information, please visit the Emisphere website,
http://www.emisphere.com.
Safe Harbor Statement Regarding Forward-looking Statements
The statements in this release and oral statements made by
representatives of Emisphere relating to matters that are not historical
facts (including without limitation those regarding the timing or potential
outcomes of research collaborations or clinical trials, any market that
might develop for any of Emisphere's product candidates and the sufficiency
of Emisphere's cash and other capital resources) are forward-looking
statements that involve risks and uncertainties, including, but not limited
to, the likelihood that future research will prove successful, the
likelihood that any product in the research pipeline will receive
regulatory approval in the United States or abroad, the ability of
Emisphere and/or its partners to develop, manufacture and commercialize
products using Emisphere's drug delivery technology, Emisphere's ability to
fund such efforts with or without partners, and other risks and
uncertainties detailed in Emisphere's filings with the Securities and
Exchange Commission, including those factors discussed under the caption
"Risk Factors" in Emisphere's Annual Report on Form 10-K (file no. 1-10615)
filed on March 5, 2007.
SOURCE Emisphere Technologies, Inc.
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Related links:
http://www.emisphere.com
CONTACT:
Investor Relations, Stewart Siskind of
Emisphere Technologies, Inc., +1-914-785-4742; or Media, Dan
Budwick of BMC Communications, +1-212-477-9007 ext. 14, for
Emisphere Technologies, Inc.
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