|
 Emisphere's
Oral Insulin Program
Emisphere Technologies, Inc. has successfully
demonstrated in clinical studies, the absorption of
insulin from the gastrointestinal tract. These
studies also demonstrated substantial reductions in
blood glucose levels following administration of an
oral formulation containing an EMISPHERE®
delivery agent in combination with insulin. The pharmacodynamic profile of the orally delivered
insulin is characterized by rapid absorption and
elimination. Clinical studies to date have shown
that the drug-carrier combination is safe with no
serious adverse events (SAE’s). The results of these
studies support our belief that a commercially
viable oral formulation of insulin can be developed.
In late 2005, Emisphere initiated a 90-day Phase II
study to evaluate the efficacy and safety of fixed
doses of oral insulin in patients with type 2
diabetes. The four-arm study evaluated the safety
and efficacy of low and high fixed doses of oral
insulin tablets versus placebo in patients with type
2 Diabetes Mellitus on existing oral metformin
monotherapy. The trial focused on the safety of oral
insulin, specifically noting incidents of
hypoglycemia, as well as the occurrence of insulin
antibodies. The efficacy component of the trial was
designed to measure changes in Hemoglobin A1c
(HbA1c) over 90 days, the standard for evaluating
glucose control in type 2 diabetics. An additional
objective was to confirm that insulin delivered
orally could be administered as a fixed dose product
without the need to conduct glucose monitoring or
titrate the insulin dose.
Due to a high variability in the screening to
baseline changes in HbA1c of the patients and
non-adherence to the original enrollment criteria
(HbA1c > 7.5), there was no statistically
significant difference in the changes in HbA1c
between the groups. However, in a subset population
analysis of patients that met the screening
criteria, there was a statistically significant
change from the placebo to the oral insulin product
in these patients as measured by their changes in
hemoglobin A1c.
Emisphere has recruited a panel of highly qualified
thought leaders in the field of diabetes to provide
recommendations on studies to be conducted to move
the program forward.
The Scientific Advisory Board (SAB) is comprised of
the
following members:
Daniel J. Drucker, M.D., FRCPC, Professor of
Medicine in the Department of Medicine, Division of
Endocrinology & Metabolism at the University of
Toronto, Canada.
Jay S. Skyler, M.D., MACP, Professor of
Medicine, Pediatrics, & Psychology, in the Division
of Endocrinology, Diabetes, & Metabolism, Department
of Medicine, University of Miami Miller School of
Medicine, Miami, Florida.
Bernard Zinman, M.D., CM, FRCPC, FACP,
Professor of Medicine at the University of Toronto,
Canada and Senior Scientist at the Samuel Lunenfeld
Research Institute, Mount Sinai Hospital.
Julio Rosenstock, M.D., Director of the
Dallas Diabetes and Endocrine Center at Medical
City, an endocrine practice and clinical research
facility and a clinical professor of medicine at the
University of Texas Southwestern Medical Center at
Dallas.
Steven E. Kahn, MB, ChB, Professor of
Medicine in the Division of Metabolism,
Endocrinology and Nutrition at the University of
Washington.
Robert A. Gelfand, M.D., Associate Clinical
Professor of Medicine at Yale University School of
Medicine and founding member of RAG Consulting, LLC.
Market Opportunity
According to the American Diabetes
Association, there are 20.8 million people in the
United States, or 7% of the population, who have
diabetes. 1.5 million new cases were diagnosed in
people aged 20 years or older in 2005. The World
Health Organization (WHO) recently compiled data
that estimates that 180 million people have diabetes
world-wide and expects that this number will double
by 2030. The estimated cost of health care to treat
diabetic patients in the US is $132 million in
medical expenditures and lost productivity or one
out of every 10 health care dollars spent in the
United States. The total health care costs of a
person with diabetes in the USA are between twice
and three times those for people without the
condition.
Advantages of Oral Insulin
Subcutaneous insulin does not reproduce the physiological delivery of insulin to the liver and systemic circulation. In a normal individual, insulin is secreted directly into the hepatic portal vein such that the liver, the primary site of action, is exposed to higher concentrations of insulin compared with the systemic circulation. Injected insulin travels to the liver via the systemic circulation so only an estimated 20% of the injected dose is available to the liver.
Physiologically, insulin is secreted very rapidly as a metabolic response to an increase in blood glucose concentrations following food intake. Injected insulin is released into the systemic circulation over a period of time at a rate that is determined by dissolution and diffusion from the subcutaneous injection site, and is independent of blood glucose concentration. Hypoglycemia can often occur when insulin is administered by injection because insulin secretion is not switched off when normal glycemia is achieved.
In contrast to injected insulin, oral insulin is delivered directly to the liver, its primary site of action, via the portal circulation. The insulin delivered to the liver moderates hepatic glucose production, a major contributor to hyperglycemia in type 2 diabetes. In theory, oral insulin should require less insulin per dose to produce the desired effect of reaching the liver. Furthermore, the amount of insulin that reaches the systemic circulation should be smaller and the peak shorter-lived than is the case with injectable insulin, thus reducing the chance of hypoglycemia.
About Insulin
Insulin is an essential hormone for the regulation of carbohydrate metabolism. The hormone is produced in the pancreas and secreted into the portal circulation for delivery directly to the liver, where it exerts a major metabolic effect. Insulin that reaches the systemic blood circulation enables glucose uptake in peripheral tissues principally the insulin-dependent tissues: muscle, and to a lesser extent, kidney.
Insulin plays a pivotal role in diabetes mellitus, a progressive disease caused by a combination of relative deficiency in the production of insulin and/or a resistance in the response of peripheral tissues to insulin. Both genetic and environmental factors (e.g., obesity, lack of exercise) appear to play significant roles in the pathogenesis of diabetes. Patients with diabetes have either insulin-dependent diabetes mellitus (type 1 diabetes) or non-insulin-dependent diabetes mellitus (type 2 diabetes).
Type 2 diabetes, previously known as adult-onset diabetes, is a metabolic disorder resulting from the body¹s inability to produce or properly utilize insulin, and typically occurs later in life. Most advanced patients in this category require insulin supplementation as their endogenous insulin production wanes. In early stages of type 2 diabetes, patients are typically managed with non-insulin oral medications, which either stimulate insulin relaease or increase insulin sensitivity in peripheral tissues. As the disease progresses, which eventually happens in the vast majority of patients, the pancreatic cells that produce insulin degenerate and die to result in complete lack of insulin, a stage when multiple daily subcutaneous injections of insulin become necessary.
|
|
|
