Dan, I got the numbers from the WLA press release, but upon re-reading it looks like I misread the figures. The 11% refered to the % of placebo patients that saw their Hb1Ac go down to 8%, not the baseline of the responders:
First Anti-Diabetic Therapy To Target The Underlying Cause of Type II Diabetes Cleared
For Marketing By The FDA
Has the Potential to Change the Lives of People With
Type II Diabetes on Insulin
MORRIS PLAINS, N.J. Jan. 30 /PRNewswire/ -- Warner-Lambert Company
announced today that Rezulin(TM) (troglitazone) tablets have been cleared for
marketing by the U.S. Food and Drug Administration. A member of the
thiazolidinedione class, also known as "insulin resistance reducers", Rezulin
is the first antidiabetes drug designed to target insulin resistance -- the
underlying cause of type II diabetes.
Rezulin is indicated for use in patients with type II diabetes currently
on insulin whose hyperglycemia is inadequately controlled (HbA1c > 8.5
percent) despite insulin therapy of over 30 units per day given as multiple
injections.
Approximately three million people with type II diabetes take daily
injected insulin, with more than 60% of these patients unable to adequately
control their blood glucose levels. Although type II diabetes is also known
as non-insulin dependent diabetes mellitus (NIDDM), about half of all NIDDM
patients take insulin. This is due to significant insulin resistance -- a
defect in the body's ability to use insulin normally. Type I diabetes is
characterized by the inability of the body to produce insulin.
"This new drug has the potential to change the lives of people with type
II diabetes who are inadequately controlled on insulin," said Jerrold Olefsky,
M.D., Professor of Medicine, Chief, Division of Endocrinology and Metabolism,
University of California, San Diego, School of Medicine. "Rezulin works by
improving insulin resistance. It provides better control of plasma glucose
levels, and at the same time offers the possibility of a reduction in insulin
injection dosage and frequency."
In insulin-taking patients with type II diabetes, Rezulin decreases serum
glucose, plasma insulin and hemoglobin A1c.
According to the American Diabetes Association (ADA) position statement
concerning the implications of the Diabetes Control and Complications Trial
(DCCT), the benefits of controlling blood glucose levels in type I patients
could also be significant for patients with type II diabetes. DCCT results
showed that lowering blood glucose concentrations slows or prevents the
development of diabetic complications in type I patients. Although patients
with type II diabetes were not part of the DCCT, the ADA states that there is
no reason to believe that the effects of better control of blood glucose
levels would not also apply to people with type II diabetes.
Clinical Studies
Rezulin has been shown to be effective in clinical trials in over
5,000 patients, some of whom have been treated with Rezulin for more than two
years. Two pivotal, double-blind, placebo-controlled multicenter studies
examined the effects of Rezulin in a total of 573 insulin-requiring type II
diabetes patients over a six-month period. On average, patients involved in
the trials had been diagnosed with diabetes for 10 to 11 years and had been
taking insulin for four to five years.
The first clinical study, 991-040, demonstrated the efficacy of Rezulin
therapy on glycemic (blood sugar) control. In this study, 30 percent of
patients treated with 200 mg Rezulin and 57 percent of patients treated with
600 mg Rezulin achieved hemoglobin A1c (HbA1c) concentrations below 8 percent
compared with 11 percent of placebo-treated patients. The HbA1c level is an
integrated measure of glucose control over the preceding three to four months.
The American Diabetes Association treatment guidelines recommend the physician
adjust therapy when HbA1c levels are greater than 8 percent with the ultimate
goal being levels of less than 7 percent.
The second clinical study, 991-068, evaluated the effects of Rezulin on
insulin dose combined with glycemic control. Rezulin not only improved
glycemic control, but at the same time, had statistically significant effects
on insulin dose. Patients treated with 200 mg and 400 mg/day of Rezulin were
able to decrease their daily insulin doses by 41 and 58 percent respectively,
compared to 14 percent on placebo.
A reduction in daily injections was also seen. Forty-one percent of
patients on 400 mg/day decreased the frequency of their insulin injections on
average from three to one per day, while 19 percent of the group taking
placebo decreased injection frequency on average from three to two injections
per day.
Insulin injections were discontinued entirely in 15 percent of patients on
400 mg/day and seven percent on 200 mg/day, compared to 1.5 percent on
placebo.
In general, Rezulin is well tolerated. Clinical studies have shown the
overall incidence and types of reactions to Rezulin to be comparable to
placebo. The most common adverse events in placebo controlled studies,
reported with Rezulin at a frequency greater than 10 percent were infection
(18 percent vs. 22 percent on placebo), headache (11 percent vs. 11 percent on
placebo), and pain (10 percent vs. 14 percent on placebo). The incidence of
withdrawals during clinical trials was similar for patients treated with
placebo or Rezulin (4%). Rezulin has only been shown to be effective in the
presence of insulin. Therefore, Rezulin should not be used in type I diabetes
or for the treatment of diabetic ketoacidosis. Rezulin should be used with
caution in patients with moderate to severe heart failure or liver disease.
Management of type II diabetes should include diet control. Caloric
restriction, weight loss and exercise are essential for the proper treatment
of the diabetic patient.
Targets Insulin Resistance Directly
Insulin resistance is a condition in which the tissues of the body fail to
respond normally to insulin. Although normal levels of insulin are produced,
the body is unable to use its own insulin to convert food into energy. As a
result, the bodies of people with insulin resistance begin secreting
abnormally high amounts of insulin to compensate for this defect. Eventually,
however, their systems can no longer properly stimulate glucose transport in
muscle and fat and suppress hepatic (liver) glucose production. Glucose that
does not reach the cells remains in the blood stream and blood sugar levels
inevitably rise, leading to type II diabetes and other diseases. Over time,
excessive blood sugar levels can severely damage the heart, blood vessels,
kidneys, eyes and nerves.
Rezulin is the first drug to work at the cellular level to improve insulin
resistance directly -- enhancing the effects of circulating insulin, without
causing the body to increase production of insulin. Rezulin achieves these
effects through direct stimulation of peripheral glucose uptake and storage as
well as through the inhibition of glucose production
in the liver. Until now, other therapies lowered blood glucose by increasing
insulin production or decreasing hepatic glucose output.
Marketed by Parke-Davis
Rezulin 200 mg and 400 mg tablets are expected to be available to
pharmacies nationwide in late March. Information on this new treatment can be
obtained by calling Parke-Davis at 800-223-0432.
Rezulin was discovered by Sankyo Company, Ltd. of Japan and co-developed
in the U.S. by Parke-Davis and the Sankyo U.S.A. Corporation. Parke-Davis
will co-promote Rezulin in the U.S. with Sankyo/Parke-Davis, a joint venture
that was announced in September.
Parke-Davis, a division of Warner-Lambert Co., is devoted to discovering,
developing, manufacturing and marketing quality pharmaceutical products. Its
central research focus is on heart disease, diabetes, stroke, anti-infectives,
central nervous system, cancer and women's healthcare. Warner-Lambert is a
worldwide company employing approximately 38,000 people, and along with
Parke-Davis is headquartered in Morris Plains, N.J.
SOURCE Warner-Lambert Company
CONTACT: Kirsten Gorsuch, 212-448-4305, or Julie Armour,
212-448-4294, both of Ketchum Public Relations; Stephen Mock,
201-540-6696, Jeffrey Baum, 201-540-2145, Leslie Hare,
201-540-4702, Media Relations, George Shields, 201-540-6916 or
John Howarth, 201-540-4874, Investor Relations, all of Warner-
Lambert; or Jerry Franz, 703-299-2054, or Kenneth Inchausti,
703-299-5506, both of the American Diabetes Association |
