Cape Town, South Africa (ots/PRNewswire) -
- First Rimonabant Trial with HbA1c as a Primary Endpoint
Sanofi-aventis announced today that new data on rimonabant, its
first-in-class cannabinoid type 1 (CB1) receptor blocker, showed that
patients with type 2 diabetes not currently treated with
anti-diabetic medications experienced significant improvements in
blood sugar control and weight as well as other risk factors such as
HDL-cholesterol (good cholesterol) and triglycerides when compared to
placebo. The study, called SERENADE, was presented today at the
International Diabetes Federation (IDF) World Diabetes Congress in
Cape Town, South Africa. SERENADE is the second study demonstrating
that rimonabant significantly improved blood sugar levels in people
with type 2 diabetes.
In the SERENADE study, treatment-naïve type 2 diabetes patients
receiving rimonabant 20mg per day for a duration of six months
significantly lowered their HbA1c levels by 0.8% from a baseline
value of 7.9 as compared to a reduction of 0.3% in the placebo group
(p=0.002). In addition, patients with an HbA1c level greater than or
equal to 8.5% at baseline, significantly reduced their HbA1c by 1.9%
with rimonabant as compared to 0.7% with placebo(p<0.0009). Over 50%
of patients in the rimonabant arm of the trial achieved HbA1c levels
below 7%, the target for good glucose control as recommended by the
American Diabetes Association (ADA)[i]. Importantly, these
improvements in blood glucose control were accompanied by significant
and clinically meaningful reductions in body weight of 6.7 kg (14.8
lbs) in patients treated with rimonabant 20 mg, while those patients
on placebo lost only 2.7 kg (5.95 lbs) (p<0.0001).
"The management of type 2 diabetes should not only focus on
controlling blood sugar levels but also improve other risk factors
such as weight, good and bad cholesterol, triglycerides and blood
pressure," said Julio Rosenstock, M.D., Director of the Dallas
Diabetes and Endocrine Center at Medical City and also Clinical
Professor of Medicine at the University of Texas Southwestern Medical
School, Dallas, Texas who was an investigator in the SERENADE trial.
"This study suggests that rimonabant can achieve improvement in blood
glucose with the added benefit of significant weight loss and
improvement in other risk factors."
Today, more than 194 million adults or 5% of adults worldwide have
been diagnosed with diabetes, with type 2 diabetes constituting
85-95% of all diabetes in developed countries[ii]. Approximately 90
percent of type 2 diabetes is attributed to people being overweight
or obese.[iii] Diabetes and obesity are often associated with other
risk factors for cardiovascular disease including high blood pressure
and unhealthy cholesterol. Worldwide, diabetes is among the leading
causes of blindness, renal failure and lower limb amputation, as well
as death through its effects on cardiovascular disease (70-80 percent
of people with diabetes die of cardiovascular disease)[ii].
Accompanying the improvements in HbA1c and weight seen in the
rimonabant arm of the SERENADE trial were improvements in multiple
cardiometabolic risk factors. Patients in the rimonabant arm
decreased their waist circumference (a measure of abdominal obesity)
by 6.1 cm (2.34 in) compared to a 2.4 cm (0.93 in) decrease for
patients on placebo (p<0.0001). HDL-cholesterol or "good" cholesterol
increased by 10.1% compared to 3.2% for patients on placebo
(p<0.0001). Triglyceride levels (bad fats in the blood) decreased by
16.3% compared to a 4.4% increase for placebo (p=0.0031). There was a
trend toward reduction in systolic blood pressure by 5 mmHg and
diastolic blood pressure by 1.2 mmHg in the rimonabant 20 mg arm
compared to a 2.2 mm Hg decrease in systolic blood pressure and an
increase of 0.1 mm Hg in diastolic pressure in the placebo arm
(p=NS). Fasting Plasma Glucose decreased by 0.9 mmol/L (16.2 mg/dL)
in the rimonabant 20 mg arm compared to a 0.1 mmol/L (1.8 mg/dL)
increase in the placebo arm (p=0.0012). Adiponectin, a protein
associated with reduced risk of diabetes and heart disease when
present in high levels, increased by 1.6 microg/mL in the rimonabant
20 mg arm compared to a decrease of 0.2 microg/mL in the placebo arm
Approximately 57% of the improvements in HbA1C (p<0.001) were
independent of the weight loss achieved, suggesting a direct effect
of rimonabant on this parameter.
The overactivity of the Endocannabinoid System (ECS) in the fat
tissue and muscle is found to promote fat accumulation and decrease
glucose uptake, which can lead to an increased risk of developing
insulin resistance and impaired glucose tolerance. By selectively
blocking CB1 receptors of the ECS, which according to animal and
human studies can be found in the brain, fat tissue, gastrointestinal
tract, pancreas, liver and muscle, rimonabant results in a decrease
in food intake, a loss of body weight, and direct improvements in
blood sugars (HbA1c), HDL-cholesterol and triglycerides.
"Some current medications for type 2 diabetes are often associated
with weight gain," said Julio Rosenstock. "The fact that blood sugar
levels were reduced along with weight loss and improvements in
HDL-cholesterol ("good" cholesterol) and triglycerides may further
support the novel mechanism of action of rimonabant, which is
different from the mode of action of current oral anti-diabetic
The most common side effects with placebo and rimonabant 20 mg
reported in the SERENADE trial were dizziness (2.1% vs. 10.9%),
nausea (3.6% vs. 8.7%), nasopharyngitis (7.9% vs. 7.2%), upper
respiratory tract infection (2.7 % vs. 7.2%), anxiety (3.6% vs.
5.8%), depressed mood (0.7% vs. 5.8%), and headache (6.4% vs. 3.6%).
The rate of serious adverse events was 3.6% for patients in the
placebo arm versus 6.5% for patients in the rimonabant 20 mg.
Overall, discontinuation rates due to adverse events in the trial
were 2.1% in placebo-treated patients versus 9.4% for patients on
rimonabant 20 mg. The most common adverse events leading to
discontinuation for the placebo and rimonabant 20 mg patients,
respectively, were nausea (0% vs. 2.2%), depressed mood disorder (0%
vs. 2.2%) and paraesthesia (0% vs. 2.2%).
SERENADE (Study Evaluating Rimonabant Efficacy in Drug-NAive
DiabEtic Patients) was a multi-centre, randomised, double-blind,
placebo-controlled, parallel-group study comparing rimonabant 20 mg
once daily to placebo in improving blood sugar control (as indicated
by HbA1c) in treatment-naive type 2 diabetic patients not adequately
controlled by diet alone for a period of six months.
The study was conducted on 278 patients at 56 study centres in the
United States, Germany, Argentina, Chile, Hungary, Poland and the
Netherlands. The primary endpoint of the trial was change from
baseline of HbA1c levels. Secondary endpoints included weight and
waist circumference, a key marker of intra-abdominal adiposity,
fasting plasma glucose, lipid parameters and arterial blood pressure.
To be included in the trial patients had to have a diagnosis of
type 2 diabetes for at least two months but less than three years,
HbA1c levels greater than 7% and less than 10%, and could not have
been treated previously with an anti-diabetic medication within six
months prior to screening.
SERENADE is part of an extensive worldwide Phase IIIb clinical
trial programme involving over 22,000 patients in eight studies,
which will investigate the role of rimonabant in the treatment of
type 2 diabetes and cardiovascular disease.
In Europe, rimonabant, known as ACOMPLIA(R) is approved as an
adjunct to diet and exercise for the treatment of obese patients (BMI
is greater than or equal to 30kg/m2), or overweight patients
(BMI>27kg/m2) with associated risk factors, such as type 2 diabetes
Rimonabant is currently commercialised in the United Kingdom,
Germany, Denmark, Sweden, Finland, Norway, Ireland, Argentina and
At the end of October 2006, sanofi-aventis submitted a complete
response to the U.S. Food and Drug Administration (FDA) approvable
letter received in February 2006.
Sanofi-aventis is the world's third largest pharmaceutical
company, ranking number one in Europe. Backed by a world-class R&D
organization, sanofi-aventis is developing leading positions in seven
major therapeutic areas: cardiovascular, thrombosis, oncology,
metabolic diseases, central nervous system, internal medicine, and
vaccines. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in
New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as defined
in the Private Securities Litigation Reform Act of 1995.
Forward-looking statements are statements that are not historical
facts. These statements include financial projections and estimates
and their underlying assumptions, statements regarding plans,
objectives and expectations with respect to future events,
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sanofi-aventis' management believes that the expectations reflected
in such forward-looking statements are reasonable, investors are
cautioned that forward-looking information and statements are subject
to various risks and uncertainties, many of which are difficult to
predict and generally beyond the control of sanofi-aventis, that
could cause actual results and developments to differ materially from
those expressed in, or implied or projected by, the forward-looking
information and statements. These risks and uncertainties include
those discussed or identified in the public filings with the SEC and
the AMF made by sanofi-aventis, including those listed under "Risk
Factors" and "Cautionary Statement Regarding Forward-Looking
Statements" in sanofi-aventis' annual report on Form 20-F for the
year ended December 31, 2005. Other than as required by applicable
law, sanofi-aventis does not undertake any obligation to update or
revise any forward-looking information or statements.
[i] American Diabetes Association. Standards of Medical Care in
Diabetes 2006. Diabetes Care 2006;29:S4-42.
[ii] The International Diabetes Federation Diabetes Atlas.
Available at: http://www.idf.org/home/index.cfm?unode=3B96906B-C026-2
FD3-87B73F80BC22682A. Last Accessed November 15th, 2006.
[iii] World Health Organization,
accessed 11/17/08 /p2/Line 63-64.
ots Originaltext: sanofi-aventis Group
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