Sanofi-aventis (Paris:SAN)(NYSE:SNY) 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=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=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=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® 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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