Paris (ots/PRNewswire) - Sanofi-aventis (EURONEXT: SAN and
NYSE: SNY) announced today that findings from the landmark ATHENA
study showed that Multaq(R) (dronedarone), a potential therapy for
the treatment of patients with atrial fibrillation or atrial flutter,
decreased the risk of cardiovascular hospitalisations or death from
any cause by a statistically significant 24% (p=0.00000002), meeting
the study's primary endpoint. The ATHENA results will be presented at
the late breaking clinical trial session of Heart Rhythm 2008, the
Heart Rhythm Society's 29th Annual Scientific Sessions in San
For the first time in twenty years of clinical drug trials in
atrial fibrillation, an investigational medicine, Multaq(R), showed a
significant decrease in the risk of cardiovascular death by 30%
(p=0.03) on top of standard therapy, including rate control and
antithrombotic drugs, in patients with atrial fibrillation or atrial
flutter. Multaq(R) also significantly decreased the risk of
arrhythmic death by 45% (p=0.01) and there were numerically fewer
deaths (16%) from any cause in the dronedarone group compared to
placebo (p=0.17). First cardiovascular hospitalisation was reduced by
25% (p=0.000000009) in the dronedarone group.
"The ATHENA results have the potential to change the face of
atrial fibrillation management. For atrial fibrillation patients, who
together with their physicians struggle on a daily basis to manage
the dramatic consequences of this complex disease, Multaq(R) carries
hope for patients" said Marc Cluzel, sanofi-aventis Senior Vice
President, R&D. "This milestone is indicative of sanofi-aventis'
commitment to bringing innovative therapies to market, and of our
ongoing commitment to provide patients, physicians and public health
stakeholders with breakthrough medicines in those therapeutic areas
where there are major healthcare needs and limited solutions".
Atrial fibrillation is a major cause of hospitalisation and
mortality and affects about 2.5 million people in the United States,
as well as 4.5 million people in the European Union and is emerging
as a growing public health concern due to an aging population.
Patients suffering from atrial fibrillation have twice the risk of
death, an increased risk of stroke and cardiovascular complications,
including congestive heart failure. Furthermore atrial fibrillation
considerably impairs patients' lives, mainly because of their
inability to perform normal daily activities due to complaints of
palpitations, chest pain, dyspnoea, fatigue or light-headedness ,
without consideration of the cumbersome and sometime serious
constraints imposed by current therapies of atrial fibrillation.
"In atrial fibrillation where treatment morbidity-mortality
benefit still needed to be demonstrated, ATHENA is a unique trial
using clinically relevant outcomes such as cardiovascular
hospitalisation or death as the primary endpoint. In this regard, the
trial has clearly achieved these safety and efficacy endpoints," said
Dr Stefan H. Hohnloser, J.W. from the Goethe University, Division of
Clinical Electrophysiology, Frankfurt, Germany, who served as
co-principal investigator of the ATHENA study. "As a consequence,
dronedarone is the first safe treatment for atrial fibrillation,
which has been demonstrated to reduce cardiovascular hospitalisation
or mortality in patients with AF" he added.
The most frequently reported adverse events of Multaq(R) vs.
placebo in the ATHENA trial were gastro-intestinal effects (26% vs.
22%), skin disorders (10% vs. 8%, mainly rash) and increased blood
creatinine (4.7% vs. 1%). The mechanism of blood creatinine increase
(inhibition of creatinine secretion at the renal tubular level) is
well defined. Compared to placebo, Multaq(R) showed a low risk of
pro-arrhythmia and no excess of hospitalisations for congestive heart
failure. There was a similar rate of study drug discontinuation
between the 2 study groups.
"ATHENA is truly a landmark trial, that marks a paradigm change
for the management of atrial fibrillation," said Dr Christopher
Cannon, a Senior Investigator in the TIMI Study Group at Brigham and
Women's Hospital, who was not involved in the study. "Atrial
fibrillation is a very common disease, and our prior treatment
options have been focused only on symptom relief and a hope to not do
harm, which has been the problem with prior antiarrhythmic drugs.
Now, with a highly significant reduction in death or hospitalisation,
as well as a 45% reduction in arrhythmic death or 30% cardiovascular
death, dronedarone may become a first line treatment of atrial
ATHENA, the largest double blind randomised study in patients
with atrial fibrillation, was conducted in more than 550 sites in 37
countries and enrolled a total of 4,628 patients. The landmark ATHENA
trial is the first morbidity-mortality study as part of the Multaq(R)
phase III clinical development program, which also included five
other multinational clinical studies, an initial study, ANDROMEDA,
conducted in patients with severe congestive heart failure and a
recent decompensation, and a total of 4 international studies in
atrial fibrillation: EURIDIS/ADONIS, ERATO, and the ongoing DIONYSOS
Based upon this new clinical data, sanofi-aventis plans to submit
a registration dossier to the European Medicines Agency (EMEA), and a
new drug application (NDA) to the U.S. Food and Drug Administration
(FDA) during the 3rd quarter of 2008.
About Atrial Fibrillation / Flutter
Atrial fibrillation is a major cause of hospitalisation and
mortality and affects about 2.5 million people in the USA and 4.5
million people in the European Union. The Atrial Fibrillation
Foundation expects the number of patients with AF to double in the
next 20 years. Without appropriate management, atrial fibrillation
can lead to serious complications, such as stroke and congestive
AF is a condition in which the upper chambers of the heart beat
in an uncoordinated and disorganised fashion, resulting in an
irregular and fast heart rhythm (i.e. an irregular heartbeat). Atrial
flutter is an abnormal fast heart rhythm that occurs in the atria of
the heart. This rhythm occurs often in individuals with other heart
conditions (e.g. pericarditis, coronary artery disease, and
cardiomyopathy). Atrial flutter frequently degenerates to atrial
fibrillation. However, it may persist for months to years.
When blood is not completely pumped out of the heart's chambers,
it can pool and clot. If a blood clot forms in the atria, it can exit
the heart and block an artery in the brain, resulting in a stroke.
Consequently, about 15 percent of all strokes result from atrial
The most common symptoms of atrial fibrillation include
palpitations (a rapid, irregular, "flopping" movement or pounding
sensation in the chest or neck), shortness of breath, dizziness and
feeling of heaviness, or constriction in the chest. The disorder may
even be more common than diagnosed, as patients may experience atrial
fibrillation episodes that either do not cause symptoms or are not
documented during their visits to the doctor.
About the ATHENA Study
The landmark ATHENA study is a randomised, placebo controlled,
international multi-center study that evaluated for the first time a
treatment on top of standard background therapy for the management of
patients with atrial fibrillation in reducing morbidity and mortality
by preventing cardiovascular hospitalisations or death from any
cause. The study included 4,628 patients, which make it the largest
ever outcome study of an anti-arrhythmic treatment for atrial
The ATHENA study objectives were to show a potential benefit of
Multaq(R) on the primary composite endpoint of all-cause mortality
combined with cardiovascular hospitalisation as compared to placebo.
The pre-specified secondary endpoints were death from any cause,
cardiovascular death and hospitalisation for cardiovascular reasons.
The pre-specified safety endpoint was the incidence of treatment
emergent adverse events (time of observation for treatment emergent
adverse events) including: all adverse events, serious adverse
events, adverse events leading to study drug discontinuation.
The atrial fibrillation or atrial flutter patients studied were
either 75 years of age or over (with or without cardiovascular risk
factor) or were below 75 years of age with at least one additional
cardiovascular risk factor (hypertension, diabetes, previous
cerebrovascular event, left atrium size greater than 50 mm or left
ventricular ejection fraction lower than 40 percent). Patients
suffering from decompensated heart failure were excluded from the
study. Patients were randomised to receive Multaq(R) 400 mg BID or
placebo, with a maximum follow-up of 30 months.
The countries which enrolled patients included: Argentina,
Australia, Austria, Belgium, Canada, Chile, China, Czech Republic,
Finland, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy,
Malaysia, Mexico, Morocco, New Zealand, Norway, Philippines, Poland,
Portugal, Russia, South Africa, Singapore, South Korea, Spain,
Sweden, Taiwan, Thailand, The Netherlands, Tunisia, Turkey, the UK,
About Multaq(R) (dronedarone)
Dronedarone (brand name Multaq(R)) is an investigational new
treatment for patients with atrial fibrillation, which has been
discovered and developed by sanofi-aventis for the prevention and
treatment of patients with atrial fibrillation or atrial flutter.
Dronedarone is a multi-channel blocker that affects calcium,
potassium and sodium channels and has anti-adrenergic properties.
Dronedarone does not contain the iodine radical and did not show any
evidence of thyroid or pulmonary toxicity in clinical trials.
About sanofi-aventis in Cardiology and Thrombosis
Sanofi-aventis' unmatched experience in the treatment of millions
of patients suffering from cardiovascular disease (CVD) and
thrombosis has uniquely prepared us to take on the growing challenges
in these domains. Today, together with academic institutions and
healthcare professionals, we are a major contributor in the effort to
reduce the public health burden across the broad CVD spectrum and in
Our comprehensive set of innovative therapeutic solutions
includes antiplatelet and antithrombotic agents with Plavix(R) and
Clexane(R)/Lovenox(R), as well the antihypertensive agent
Aprovel(R)/Avapro(R ). By listening and responding to the needs of
patients and physicians, we constantly seek to improve the safety and
efficacy of our products while developing new therapeutic strategies.
Our dedication has already helped lay the foundations of modern
cardiovascular treatment. In addition to the first-in-class
ticlopidine, we pioneered treatment with amiodarone and heparins,
therapies rooted in a deep legacy of research experience spanning
Building on our deep foundations of experience and expertise, we
are seeking improved treatment efficacy with new ultra-low-weight
heparins (AVE5026), with a new reversible, long-acting anticoagulant,
potentially better-suited for venous thromboembolism and atrial
fibrillation (biotinylated Idraparinux). Our research into atrial
fibrillation continues with ground breaking trials like ATHENA with
the clinical development of dronedarone (Multaq(R)). We are
simultaneously exploring targeted gene therapy (NV1FGF) with the aim
of reducing the risk of amputation in patients with critical ischemia
of the lower limbs. As we continue to push the frontiers of
cardiovascular and thrombosis therapy, we do so with the conviction
that the health of patients is our total commitment and our greatest
Sanofi-aventis, a leading global pharmaceutical company,
discovers, develops and distributes therapeutic solutions to improve
the lives of everyone. 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, as amended.
Forward-looking statements are statements that are not historical
facts. These statements include product development, product
potential projections and estimates and their underlying assumptions,
statements regarding plans, objectives, intentions and expectations
with respect to future events, operations, products and services, and
statements regarding future performance. Forward-looking statements
are generally identified by the words "expects," "anticipates,"
"believes," "intends," "estimates," "plans" and similar expressions.
Although 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 among other things, the uncertainties inherent
in research and development, future clinical data and analysis,
including post marketing, decisions by regulatory authorities, such
as the FDA or the EMEA, regarding whether and when to approve any
drug, device or biological application that may be filed for any such
product candidates as well as their decisions regarding labelling and
other matters that could affect the availability or commercial
potential of such products candidates, the absence of guarantee that
the products candidates if approved will be commercially successful,
the future approval and commercial success of therapeutic
alternatives as well as 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, 2007. Other than as required by
applicable law, sanofi-aventis does not undertake any obligation to
update or revise any forward-looking information or statements.
ots Originaltext: sanofi-aventis Group
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