BRIDGEWATER, N.J., May 15 /PRNewswire-FirstCall/ -- Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that findings from the landmark ATHENA study showed Multaq(R) (dronedarone), a potential therapy for the treatment of patients with atrial fibrillation or atrial flutter, decreased the risk of cardiovascular hospitalizations or death from any cause by a statistically significant 24% (p=0.00000002), meeting the study 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(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 for arrhythmic death by 45% (p=0.01), and there were numerically less deaths (16%) from any cause in the dronedarone group compared to placebo (p=0.17). First cardiovascular hospitalization 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 hospitalization 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 because of the aging of the 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 hospitalization 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 potential treatment for atrial fibrillation, which was demonstrated in the ATHENA trial to reduce cardiovascular hospitalization or mortality in patients with AF," he added.
The most frequently reported adverse events of Multaq(R) vs. placebo induced gastro-intestinal effect (26% vs. 22%), skin disorder (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) was well defined, in a separate study of healthy volunteers. Multaq(R) showed a rate of pro-arrhythmia similar to placebo and no excess of hospitalizations 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 potential 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 the ATHENA study demonstrating a highly significant reduction in death or hospitalization, as well as a 45% reduction in arrhythmic death or 30% cardiovascular death, dronedarone may become an appropriate treatment option for atrial fibrillation."
ATHENA, the largest double blind randomized 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 ATHENA landmark 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 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 hospitalization 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 disorganized 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 randomized, placebo controlled, international metacentre 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 hospitalizations or death from any cause. The study included 4,628 patients, which made 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(R) on primary composite endpoint of all-cause mortality combined with cardiovascular hospitalization as compared to placebo. The pre-specified secondary endpoints were death from any cause, cardiovascular death and hospitalization 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 patient population studied were either greater than or equal to 75 years (with or without cardiovascular risk factor) or were <75 years with at least one additional cardiovascular risk factor (hypertension, diabetes, previous cerebrovascular event, left atrium size >50 mm or left ventricular ejection fraction <40 percent). Patients suffering from decompensated heart failure were excluded from the study. Patients were randomized 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, the US.
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 thrombosis.
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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Marisol Peron, sanofi-aventis
Amy Ba, sanofi-aventis
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