Isis
Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today positive Phase 2
results in patients with type 2 diabetes treated with ISIS 113715 as a
single-agent. An intent-to-treat analysis of all patients enrolled in the
trial treated with 200 mg/wk for three months showed statistically
significant improvement in multiple measures of glucose control. ISIS
113715 did not cause hypoglycemia (low blood sugar), did not cause weight
gain and was well tolerated. ISIS 113715, a second-generation antisense
drug, is a novel insulin sensitizer that reduces the expression of protein
tyrosine phosphatase-1B (PTP-1B). PTP-1B is a mediator of insulin
resistance, one of two main defects in patients with type 2 diabetes.
The randomized, double-blind, placebo-controlled Phase 2 study was
conducted in newly diagnosed type 2 diabetic patients with moderate
diabetes (average HbA1c approximately 8%, average fasting glucose levels
approximately 160 mg/dL). The study was divided into two parts, a
dose-escalation portion designed primarily to assess the safety of 6 weeks
of dosing with ISIS 113715 at weekly doses of 100, 200, 400 and 600 mg, and
a 3 month dosing group at 200 mg/week designed to determine the effects of
treatment with ISIS 113715 on several measures of blood glucose control.
Because patients in the study were newly diagnosed and had never received
drug treatment for diabetes, both placebo and drug treated patients
exhibited reductions in glucose levels as a result of improved diet and
medical care. However, after 3 months of treatment, patients treated with
200 mg/week of ISIS 113715 showed consistent improvement from baseline in
several indices of blood glucose control. Reduction in several of these
indices was statistically significant as compared to placebo treated
subjects. In addition, patients treated with ISIS 113715 achieved
statistically significant reductions in cholesterol levels secondary to
reductions in PTP-1B.
"The results from this study are quite encouraging as ISIS 113715
appears to be effective in improving blood glucose control in patients with
type 2 diabetes," said Robert Henry, M.D., Professor of Medicine at the
University of California, San Diego and Chief, Section of Diabetes,
Endocrinology, and Metabolism at VA San Diego Healthcare System. "If these
data are confirmed in larger studies, ISIS 113715 has the potential to be
an important new drug for the treatment of patients with type 2 diabetes.
Type 2 diabetes represents a rapidly growing population in desperate need
of new therapies. With the limitations of current therapies, there is a
great need to develop drugs with new mechanisms that can alter the course
of the disease or offer multiple metabolic benefits."
In the dose-escalation safety portion of the trial, patients (n=66)
were treated for 6 weeks at doses of 100, 200, 400, or 600 mg. The
highlights of the safety portion of the study are:
-- No drug related serious adverse events
-- No hypoglycemia, weight gain or metabolic acidosis
-- No clinically significant alterations in kidney or liver function
-- Dose dependent reduction of fasting blood glucose levels (-21mg/dL,
p=0.05 at 600 mg/week)
?? Dose dependent reduction of LDL cholesterol (-17 mg/dL, p=0.02 at 600 mg/week)
"Having completed the analysis of all the patients in this study
through the treatment period, we have shown that reducing PTP-1B expression
with ISIS 113715 resulted in significant improvement in glucose control in
patients with type 2 diabetes and was well tolerated," said Sanjay Bhanot,
M.D., Ph.D., Vice President of Metabolic Diseases Research and Development
at Isis Pharmaceuticals. "ISIS 113715 improves glucose control as a
single-agent without the side effects observed with existing drugs and also
has a favorable effect on cholesterol. In addition to measuring fasting
glucose levels, we measured postprandial blood glucose levels in a group of
patients. Consistent with our other measurements, we also observed
improvements in postprandial glucose control. These benefits make ISIS
113715 a very exciting drug."
"The results from this study support our enthusiasm about our recently
initiated study to examine ISIS 113715 in combination with other
antidiabetic drugs," Dr. Bhanot added. "We continue to be encouraged by the
data from our cardiovascular and metabolic programs, including the recently
reported Phase 2 data from our cholesterol lowering drug, ISIS 301012.
These data reinforce our excitement about our pipeline and the value of our
antisense platform."
ABOUT MEASURES OF BLOOD GLUCOSE CONTROL
The measures of blood glucose control in this Phase 2 study were HbA1c
levels, fasting glucose levels (both self-monitored with a glucometer and
those measured by the treating physicians) and postprandial glucose levels
(glucose testing after meals). HbA1c is a measure that reflects the average
blood glucose levels over a 3 month period, and is one of the standard
measures used by physicians to tell if a patient's blood sugar is under
control. The American Diabetes Association has established a HbA1c
measurement of 7% or less as the target for effective glucose control.
ABOUT ISIS 113715
ISIS 113715, a second-generation antisense drug, inhibits PTP-1B, an
enzyme that is a key mediator of insulin resistance. Insulin resistance is
one of two main defects in patients with type 2 diabetes. The inhibition of
PTP-1B may allow insulin receptors to stay active longer, allowing for more
sugar uptake into cells, and thereby lowering blood sugar levels in the
bloodstream. ISIS 113715 may offer new treatment to patients who do not
respond adequately to currently available therapies such as glitazones,
sulfonylureas, and biguanides.
Data from the single-agent Phase 2 study reported today in
newly-diagnosed diabetic patients validate PTP-1B as a target for the
treatment of type 2 diabetes that may also have ancillary therapeutic
benefits of value to these diabetic patients. ISIS 113715 was
well-tolerated. These data support the safety and efficacy for continued
development of ISIS 113715 for patients with type 2 diabetes.
Isis recently initiated a combination study of ISIS 113715 in patients
with type 2 diabetes. The Phase 2 dose-escalation study will evaluate the
safety and activity of ISIS 113715 in combination with oral antidiabetic
drugs. In this study, ISIS 113715 will be administered in patients with
type 2 diabetes being treated with sulfonylurea or with sulfonylurea and
metformin over a 13 week treatment period. In addition, Isis is conducting
a Phase 2 study of ISIS 113715 in patients with type 2 diabetes at Yale
University to further assess the effects of ISIS 113715 on insulin
sensitivity, fasting and postprandial glucose control and lipid metabolism.
In Phase 1 trials, ISIS 113715 increased insulin sensitivity in healthy
volunteers. In preclinical studies, ISIS 113715 normalized blood sugar
levels in multiple rodent models and improved glucose tolerance in normal
and obese primates. ISIS 113715 has not produced hypoglycemia or weight
gain, characteristics of many other type 2 diabetes treatments in animals
and in human clinical studies to date.
ABOUT TYPE 2 DIABETES
Type 2 diabetes is the most common form of diabetes. In type 2
diabetes, either the body does not produce enough insulin or the cells do
not respond to insulin. Insulin is necessary for the body to be able to use
sugar. Sugar is the basic fuel for the cells in the body, and insulin takes
the sugar from the blood into the cells. When glucose builds up in the
blood instead of going into cells, it can cause two problems: cells may be
starved for energy or over time, high blood glucose levels may affect the
eyes, kidneys, nerves or heart. According to the American Diabetes
Association, diabetes affects nearly 17 million people and type 2 diabetes
constitutes 90 percent of those cases.
WEBCAST PRESENTATION INFORMATION
Isis will conduct a live webcast presentation with slides to discuss
this press release Tuesday, June 13 at 12:00 pm Eastern time. To
participate over the Internet go to
investorcalendar/ClientPage.asp?ID=105099 or
isispharm. A replay of the webcast will be available at
these addresses for a limited time.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting its expertise in RNA to discover and develop novel
drugs for its product pipeline and for its partners. The Company has
successfully commercialized the world's first antisense drug and has 15
drugs in development. Isis' drug development programs are aimed at treating
cardiovascular, metabolic and inflammatory diseases. Isis' partners are
focused in disease areas such as inflammatory, ocular, viral and
neurodegenerative diseases, and cancer. In its Ibis division, Isis is
developing and commercializing the IBIS biosensor system, a revolutionary
system to identify infectious organisms. As an innovator in RNA-based drug
discovery and development, Isis is the owner or exclusive licensee of
approximately 1,500 issued patents worldwide. Additional information about
Isis is available at isispharm.
This press release includes forward-looking statements regarding the
therapeutic and commercial potential of ISIS 113715 for the treatment of
type 2 diabetes. Any statement describing Isis' goals, expectations,
intentions or beliefs is a forward-looking statement and should be
considered an at-risk statement, including those statements that are
described as Isis' goals. Such statements are subject to certain risks and
uncertainties, particularly those inherent in the process of discovering,
developing and commercializing drugs that are safe and effective for use as
human therapeutics, and in the endeavor of building a business around such
products. Isis' forward-looking statements also involve assumptions that,
if they never materialize or prove correct, could cause its results to
differ materially from those expressed or implied by such forward-looking
statements. Although Isis' forward-looking statements reflect the good
faith judgment of its management, these statements are based only on facts
and factors currently known by Isis. As a result, you are cautioned not to
rely on these forward-looking statements. These and other risks concerning
Isis' programs are described in additional detail in Isis' annual report on
Form 10-K for the year ended December 31, 2005, and its quarterly report on
Form 10-Q for the quarter ended March 31, 2006, which are on file with the
SEC. Copies of these and other documents are available from the Company.
Isis Pharmaceuticals, Inc.
isispharm
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