Landmark ATHENA Study Findings With Multaq(R)(dronedarone) Show 24%
Reduction in Cardiovascular Hospitalisation or Death in Patients With
Atrial Fibrillation
PARIS, FRANCE--(Marketwire - May 15, 2008) - Sanofi-aventis (NYSE:
SNY) (EURONEXT: SAN) announced today that findings from the landmark
ATHENA study showed that Multaq® (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 equals
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 Francisco, USA.
For the first time in twenty years of clinical drug trials in atrial
fibrillation, an investigational medicine, Multaq®, showed a
significant decrease in the risk of cardiovascular death by 30% (p
equals 0.03) on top of standard therapy, including rate control and
antithrombotic drugs, in patients with atrial fibrillation or atrial
flutter. Multaq® also significantly decreased the risk of arrhythmic
death by 45% (p equals 0.01) and there were numerically fewer deaths
(16%) from any cause in the dronedarone group compared to placebo (p
equals 0.17). First cardiovascular hospitalisation was reduced by 25%
(p equals 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® 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® 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® 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
fibrillation".
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®
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
trial.
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 heart
failure.
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
fibrillation.
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
fibrillation.
The ATHENA study objectives were to show a potential benefit of
Multaq® 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® 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, the US.
About Multaq® (dronedarone)
Dronedarone (brand name Multaq®) 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 thrombosis.
Our comprehensive set of innovative therapeutic solutions includes
antiplatelet and antithrombotic agents with Plavix® and
Clexane®/Lovenox®, as well the antihypertensive agent
Aprovel®/Avapro®. 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
decades.
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®). 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
reward.
About sanofi-aventis
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).
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Contacts:
Sanofi-aventis
Salah Mahyaoui
+33 (0)6.73.68.78.88
Email: salah.mahyaoui@sanofi-aventis.com