PARSIPPANY, NJ -- 05/30/08 --
Daiichi Sankyo, Inc., announced today that
data from post-hoc analyses of three pivotal studies demonstrated that the
addition of Welchol(TM), (colesevelam HCl) to common diabetes treatment
regimens can lower A1C in patients with type 2 diabetes mellitus by 1% or
greater. The analyses included all patients receiving Welchol in these
studies (n=512). Almost half (47%) of the patients in the analyses had a
mean reduction in A1C of 1.04% and nearly a quarter (24%) had a mean
reduction as great as 1.40%. Type 2 diabetes can put people at risk for
serious health complications such as blindness, amputation and kidney
failure.(1)
A second post-hoc analysis demonstrated that Welchol lowered A1C and
LDL-cholesterol (LDL-C) levels consistently across type 2 diabetes
patients, regardless of age, gender or race. These findings were included
among five poster presentations by Daiichi Sankyo at the National Lipid
Association (NLA) Annual Scientific Sessions.
The American Diabetes Association (ADA) recommends that people with type 2
diabetes control both blood glucose and cholesterol levels to reduce the
risk of developing cardiovascular disease.(2) The National Cholesterol
Education Program (NCEP) recommends that patients with type 2 diabetes keep
their cholesterol levels in check and target an LDL-C goal of < 100
mg/dL.(3) Despite this recommendation, nearly 40 percent of patients with
type 2 diabetes have LDL-cholesterol levels greater than 130 mg/dL.(4)
Welchol is the first and only therapy approved to treat both type 2
diabetes and high LDL-cholesterol.
"These findings are significant given the critical importance of achieving
and maintaining A1C control," said Vivian A. Fonseca, Professor of Medicine
and Pharmacology and Chief, Section of Endocrinology, Tulane University
Health Sciences Center, and a principal study investigator. "A patient's
A1C level is one of our primary markers in determining their risk of
developing cardiovascular disease. These analyses show that adding Welchol
to the most common type 2 diabetes regimens can help achieve additional A1C
lowering across many different patient types."
Several mechanisms have been proposed for the glucose-lowering effect of
Welchol, including reductions in glucose absorption and effects on glucose
metabolism via nuclear receptors in the intestine and/or the liver. The
exact mechanism(s) is under investigation.
About the Analyses
For both analyses, data was extracted from three double-blind,
placebo-controlled, pivotal Welchol trials involving 1,018 patients.
Welchol was added to either metformin-, insulin- or sulfonylurea-based
therapy in patients with inadequately controlled type 2 diabetes (A1C 7.5%
to 9.5%). The mean baseline A1C of patients in these studies was 8.1% to
8.3%. The primary endpoint in the pivotal Welchol trials was mean change
from baseline in A1C. Mean change in LDL-cholesterol was a secondary
endpoint.
In the first post-hoc analysis, efficacy parameters included change from
baseline in A1C. All patients receiving Welchol were pooled (N=512) and
stratified based on individual A1C reductions (greater than or equal to
0.5%, greater than or equal to 0.7%, and greater than or equal to 1.0%)
from baseline to study end. The results from the post-hoc analyses found
that almost half (47%) of the patients achieving a reduction of greater
than or equal to 0.5% had a mean A1C reduction of 1.04% (P < 0.001); 36% of
patients achieving a reduction of greater than or equal to 0.7% had a mean
A1C reduction of 1.20% (P < 0.001); and 24.1% achieving a reduction of
greater than or equal to 1.0% had a mean A1C reduction of 1.40% (P <
0.001).
In the second post-hoc analysis, data from the pivotal studies were pooled
and patients were stratified by age (greater than or equal to 65 and less
than 65 years), gender, and race (Caucasian, Black, and Hispanic).
Efficacy parameters included reductions in A1C and LDL-C across these
subgroups.
Patients aged 65 or older had a 0.59% mean reduction in A1C (P < 0.0001)
and a mean reduction in LDL-C of 14.73 (P < 0.0001), whereas patients
younger than 65 had a 0.54% mean reduction in A1C (P < 0.0001) and a mean
reduction in LDL-C of 15.50 (P < 0.0001). Regarding gender, male patients
had a 0.60% mean reduction in A1C (P < 0.0001) and a mean reduction in
LDL-C of 14.49 (P < 0.0001), while female patients had a mean reduction in
A1C of 0.48% (P < 0.0001) and a mean LDL-C reduction of 16.13% (P <
0.0001).
When patients were stratified by race, all subgroups had comparable
reductions in both A1C and LDL-C: Caucasian patients had a mean reduction
in A1C of 0.48% (P < 0.0001) and a mean reduction in LDL-C of 16.16 (P <
0.0001); Black patients had a 0.77% mean reduction in A1C (P < 0.0002) and
a mean reduction in LDL-C of 19.64 (P < 0.0001); and Hispanic patients had
a 0.54% mean reduction in A1C (P < 0.0001) and a mean reduction in LDL-C of
11.31 (P < 0.0001).
IMPORTANT INFORMATION ABOUT WELCHOL
Welchol is indicated as an adjunct to diet and exercise to reduce elevated
low-density lipoprotein cholesterol (LDL-C) in patients with primary
hyperlipidemia (Fredrickson Type IIa) as monotherapy or in combination with
an hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor. Welchol
is also indicated as an adjunct to diet and exercise to improve glycemic
control in adults with type 2 diabetes mellitus.
Welchol should not be used for the treatment of type 1 diabetes or for the
treatment of diabetic ketoacidosis. It has not been studied in type 2
diabetes as monotherapy or in combination with a dipeptidyl peptidase 4
inhibitor and has not been extensively studied in combination with
thiazolidinediones. Welchol has not been studied in Fredrickson Type I,
III, IV, and V dyslipidemias.
Welchol is contraindicated in individuals with bowel obstruction, those
with serum triglyceride (TG) concentrations of > 500 mg/dL, or with a
history of hypertriglyceridemia-induced pancreatitis.
The effect of Welchol on cardiovascular morbidity and mortality has not
been determined. Welchol can increase serum TG concentrations particularly
when used in combination with sulfonylureas or insulin. Caution should be
exercised when treating patients with TG levels > 300 mg/dL.
Welchol may decrease the absorption of fat-soluble vitamins A, D, E, and K.
Patients on vitamin supplements should take their vitamins at least 4 hours
prior to Welchol. Caution should be exercised when treating patients with a
susceptibility to vitamin K or fat soluble vitamin deficiencies.
Caution should also be exercised when treating patients with gastroparesis,
gastrointestinal motility disorders, major gastrointestinal tract surgery,
and when treating patients with dysphagia and swallowing disorders.
Welchol reduces gastrointestinal absorption of some drugs. Drugs with a
known interaction with colesevelam (glyburide, levothyroxine, and oral
contraceptives [ethinyl estradiol, norethindrone]) should be administered
at least 4 hours prior to Welchol. Drugs that have not been tested for
interaction with colesevelam, especially those with a narrow therapeutic
index, should also be administered at least 4 hours prior to Welchol.
Alternatively, the physician should monitor drug levels of the
co-administered drug.
Primary Hyperlipidemia: In clinical trials, the adverse reactions observed
in greater than or equal to 2% of patients -- and more commonly with
Welchol than placebo -- regardless of investigator assessment of causality
were constipation (11.0% vs. 7.0%), dyspepsia (8.3% vs. 3.5%), nausea (4.2%
vs. 3.9%), accidental injury (3.7% vs. 2.7%), asthenia (3.6% vs. 1.9%),
pharyngitis (3.2% vs. 1.9%), flu syndrome (3.2% vs. 3.1%), rhinitis (3.2%
vs. 3.1%) and myalgia (2.1% vs. 0.4%).
Type 2 Diabetes: In clinical trials, the adverse reactions observed in
greater than or equal to 2% of patients -- and more commonly with Welchol
than placebo -- regardless of investigator assessment of causality were
constipation (8.7% vs. 2.0%), nasopharyngitis (4.1% vs. 3.6%) dyspepsia
(3.9% vs. 1.4%), hypoglycemia (3.0% vs. 2.3%), nausea (3.0% vs. 1.4%) and
hypertension (2.8% vs. 1.6%).
Post-marketing experience: Due to the voluntary nature of these reports it
is not possible to reliably estimate frequency or establish a causal
relationship. Increased seizure activity or decreased phenytoin levels have
been reported in patients receiving phenytoin concomitantly with Welchol.
Reduced International Normalized Ratio (INR) has been reported in patients
receiving warfarin concomitantly with Welchol.
Welchol is Pregnancy Category B.
For more information on Welchol, call 877-4-DSPROD (877-437-7763), or go to
the Welchol web site at www.Welchol.com.
About Daiichi Sankyo, Inc.
Daiichi Sankyo, Inc., headquartered in Parsippany, New Jersey, is the U.S.
subsidiary of Daiichi Sankyo Co., Ltd., one of Japan's leading
pharmaceutical companies and a global leader in pharmaceutical innovation
whose roots date back to 1899. The company is dedicated to the discovery,
development and commercialization of innovative medicines that improve the
lives of patients throughout the world. The primary focus of Daiichi
Sankyo's research and development is cardiovascular disease, including
therapies for dyslipidemia, hypertension, diabetes, and acute coronary
syndrome. The company is also pursuing the discovery of new medicines in
the areas of glucose metabolic disorders, infectious diseases, cancer, bone
and joint diseases, and immune disorders. For more information, visit
www.dsus.com.
References:
(1) American Diabetes Association, Type 2 Diabetes
Complications. http://www.diabetes.org/type-2-diabetes/complications.jsp.
Site Accessed 5/20/08
(2) The American Diabetes Association, Lowering Cholesterol in Patients
with Diabetes and Dyslipidemia.
http://www.diabetes.org/diabetes-research/summaries/parris-cholesterol.jsp.
Last accessed on May 9, 2008.
(3) Grundy SM, Cleeman JI, Merz CN, Brewer HB, Jr., Clark LT, Hunninghake
DB, et al. Implications of recent clinical trials for the National
Cholesterol Education Program Adult Treatment Panel III guidelines.
Circulation 110: 227-239, 2004
(4) 2004 National Healthcare Quality Report, Agency for Healthcare,
Research and Quality. United States Department of Health and Human
Services.
For more information, please contact:
Kimberly Wix
Daiichi Sankyo, Inc.
Office: 973 695 8338
Cell: 908 656 5447
kwix@dsus.com
Rich Salem
Daiichi Sankyo, Inc.
Office: 973 695 8330
Cell: 973 563 1086
rsalem@dsus.com
