PARSIPPANY, NJ -- 05/16/08 --
Daiichi Sankyo, Inc. (DSI) announced today
that data from two pooled analyses further demonstrate that Welchol(TM)
(colesevelam HCl), in combination with metformin -- or sulfonylurea-based
therapy, significantly lowers blood glucose (as measured by A1C) in
patients with type 2 diabetes mellitus who had failed to achieve glycemic
control (ADA target of A1C < 7%). These findings, presented at the American
Association of Clinical Endocrinologists' (AACE) 17th Annual Meeting and
Clinical Congress, are the latest in a series of diabetes-related
milestones for Welchol. In April, DSI announced that Welchol was added to
the American College of Endocrinology (ACE)/AACE "Road Maps to Achieve
Glycemic Control in Type 2 Diabetes Mellitus."
The efficacy of Welchol compared to placebo was evaluated in patients
receiving metformin-based or sulfonylurea-based therapy (either monotherapy
or in combination with other antidiabetes therapy) in two separate pooled
analyses of patients from three Welchol pivotal studies.* The addition of
Welchol in patients on established metformin-based therapy demonstrated a
significant mean A1C reduction of 0.50%, placebo-corrected change from
baseline (mean baseline A1C was 8.2% for both Welchol and placebo). In a
second pooled analysis, the addition of Welchol in patients on established
sulfonylurea-based therapy demonstrated a mean reduction in A1C of 0.53%,
placebo-corrected change from baseline (mean baseline A1C was 8.2% and 8.3%
for Welchol and placebo, respectively).
"These analyses further demonstrate the potential benefit of adding Welchol
to current common diabetes treatment regimens," said Vivian E. Fonseca,
Professor of Medicine and Pharmacology and Chief, Section of Endocrinology,
Tulane University Health Sciences Center, a principal investigator of the
study. "This gives physicians an additional option when it comes to
helping their patients lower their A1C levels."
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 and remains to be confirmed.
About the Analyses
A pooled analysis evaluated 696 patients on metformin-based therapy
(monotherapy or combination with other antidiabetes agents) who received
add-on treatment with Welchol 3.75 g/day (n=355) or placebo (n=341).
Efficacy endpoints in this analysis included change from baseline in A1C
and fasting plasma glucose (FPG). Lipids and weight were not analyzed in
this pooled analysis; however, LDL-C was significantly reduced in each of
the primary studies (P < 0.001 vs. placebo). Weight did not significantly
change with Welchol in any of the primary studies. The addition of Welchol
to metformin-based therapy achieved a significant mean reduction in A1C
levels of 0.42% while A1C increased by 0.08% in the placebo group,
resulting in a placebo-corrected mean change from baseline of -0.50% (P <
0.001). Fasting plasma glucose decreased by -4.6 mg/dL in the Welchol group
and increased by 11.1 mg/dL in the group treated with placebo, resulting in
a mean treatment difference of -15.7 mg/dL (P < 0.001). Furthermore, the
addition of Welchol to metformin therapy resulted in a significantly higher
proportion of patients achieving a mean reduction in A1C of greater than or
equal to 0.7% (38.3% vs. 19.4%; P < 0.001) or a reduction in FPG greater
than or equal to 30 mg/dL (30.1% vs. 22.0%; P=0.015), from baseline to
endpoint versus the placebo.
A second pooled analysis evaluated 653 patients on sulfonylurea-based
therapy (monotherapy or combination with other antidiabetes agents).
Patients received add-on therapy with Welchol 3.75 g/day (n=326) or placebo
(n=327). The addition of Welchol resulted in a mean A1C change from
baseline of -0.35% (mean baseline A1C 8.2%) compared with placebo which had
a mean increase of 0.18% (mean baseline A1C 8.3%), resulting in a mean
treatment difference of -0.53% by study end (P < 0.001). Fasting plasma
glucose decreased by -1.4 mg/dL in the patients treated with Welchol and
increased by 12.2 mg/dL in the placebo group, resulting in a mean treatment
difference of -13.6 mg/dL (P < 0.001). In addition, significantly more
patients in the Welchol treatment group achieved a reduction in A1C greater
than or equal to 0.7% (35.0% vs. 16.5%; P < 0.001) or FPG greater than or
equal to 30 mg/dL (29.1% vs. 21.7%; P=0.029), from baseline to endpoint
versus the placebo group.
Welchol Added to AACE Road Maps
Daiichi Sankyo also recently announced that Welchol has been added to the
American College of Endocrinology (ACE) and American Association of
Clinical Endocrinologist's (AACE) 2008 "Road Maps to Achieve Glycemic
Control in Type 2 Diabetes Mellitus." The Road Maps are updated regularly
by ACE/AACE to provide physicians with the latest and most comprehensive
treatment options for their patients with type 2 diabetes mellitus.
Welchol is the first and only therapy approved to treat both type 2
diabetes and high LDL-cholesterol. This is the second major diabetes
related milestone for Welchol this year, as Welchol was approved by the FDA
for the treatment of type 2 diabetes in January.
"Welchol offers physicians a new treatment option that addresses two
cardiovascular risk factors, high LDL-cholesterol and blood glucose in
patients with type 2 diabetes," said Sukumar Nagendran, M.D., Senior
Director, Diabetes and Metabolism, Daiichi Sankyo, Inc. "Cardiovascular
risk factors are always of great concern to physicians treating type 2
diabetes patients, as they are at significantly greater risk for developing
cardiovascular disease. The inclusion of Welchol in these Road Maps will
enable more physicians to be aware of the potential impact of adding this
unique product to their patients' treatment regimen."
It is estimated that half of all Americans have elevated blood cholesterol
levels that can negatively impact their health and quality of life.(1)
According to the National Healthcare Quality Report, nearly 40 percent of
adults with high cholesterol also have type 2 diabetes.(2)
The ADA recommends that patients with type 2 diabetes target an A1C level
of < 7 percent.(3) A1C is a common test for persistent hyperglycemia ("too
much glucose in the blood"). Additionally, 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.(4) Despite this recommendation, nearly 40 percent of patients with
type 2 diabetes have LDL-cholesterol levels greater than 130 mg/dL.(5)
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.
*For further information on Welchol clinical studies, please see
prescribing information.
References
(1) The American Heart Association, Cholesterol Statistics.
http://www.americanheart.org/presenter.jhtml?identifier=536.
Accessed August 24, 2007.
(2) 2004 National Healthcare Quality Report, Agency for Healthcare,
Research and Quality. United States Department of Health and Human
Services.
(3) American Diabetes Association: Standards of medical care in diabetes --
2006. Diabetes Care 29(Suppl 1):S4-S42,2006
(4) 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
(5) 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
