FDA Approves Multaq for Patients With Atrial Fibrillation or Atrial Flutter

FDA Approves Multaq(R) for Patients With Atrial Fibrillation or Atrial Flutter

Multaq(R) Approved to Reduce the Risk of Cardiovascular Hospitalizationin Patients With Atrial Fibrillation or Atrial Flutter.

PARIS, July 2 /PRNewswire/ --

- U.S Commercial Launch Planned for the Summer of 2009

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that theU.S. Food and Drug Administration (FDA) has approved Multaq(R) (dronedarone)400 mg Tablets. Patients with atrial fibrillation (AF) or atrial flutter(AFL) soon will have a new treatment option to help improve currentmanagement of their disease. Multaq(R) is the first drug approved in theUnited States that has shown a clinical benefit to reduce cardiovascularhospitalization in patients with AF/AFL.

Multaq(R) is an anti-arrhythmic indicated to reduce the risk ofcardiovascular hospitalization in patients with paroxysmal or persistentatrial fibrillation (AF) or atrial flutter (AFL), with a recent episode ofAF/AFL and associated cardiovascular risk factors, who are in sinus rhythm orwho will be cardioverted. Associated cardiovascular risk factors include ageover 70 years, hypertension, diabetes, prior cerebrovascular accident, leftatrial diameter greater than or equal to 50 mm or left ventricular ejection fraction [LVEF] <40%. The FDA approval is based on five international, multi-center, randomized clinical trials involving nearly 6,300 patients.

"The FDA approval of Multaq(R) is an important milestone in themanagement of atrial fibrillation or atrial flutter that demonstrates thecommitment of sanofi-aventis to provide patients and physicians withimportant new medicines in therapeutic areas with significant healthcareneeds," said Christopher A. Viehbacher, Chief Executive Officer ofsanofi-aventis. "Sanofi-aventis is proud of its ability to bring innovativetherapies to market and contribute to reducing the public health burden ofatrial fibrillation."

The landmark ATHENA trial evaluated the efficacy and safety of Multaq(R)in patients with AF/AFL or a recent history of these conditions (71% of thesepatients had no heart failure, 29% were in NYHA class I-III with stable heartfailure). This trial showed that Multaq(R) (dronedarone) 400 mg BID, inaddition to standard therapy, reduced the combined endpoint of cardiovascularhospitalization or death from any cause by 24% (p<0.001) when compared toplacebo, meeting the study's primary endpoint.

This reduction was generally consistent across study subgroups based onbaseline characteristics or medications. Patients taking Multaq(R) had higherrates of diarrhea, nausea, bradycardia, QT-interval prolongation andcutaneous rash than patients taking placebo.

Initiation of Multaq(R) treatment is contraindicated in patients withsevere heart failure (NYHA class IV) or NYHA Class II - III heart failurewith a recent decompensation requiring hospitalization or referral to aspecialized heart failure clinic. This unstable population corresponds to thepopulation of the ANDROMEDA trial in which patients receiving dronedarone hada greater than 2-fold increase in mortality compared to placebo.

The ATHENA and ANDROMEDA trials provided two sets of data supporting theassessment of the product's benefit risk ratio in two significantly differentpatient populations.

To ensure the use of Multaq(R) in the appropriate patient population,sanofi-aventis U.S. LLC also announced the launch of mPACT(TM) - Multaq(R)Partnership for Appropriate Care and Treatment - the Risk Evaluation andMitigation Strategy (REMS) developed by sanofi-aventis U.S. LLC. ThemPACT(TM) Partnership was developed to assist healthcare professionals (HCPs)with the identification of appropriate patients and to ensure the safe use ofMultaq(R) while minimizing risk. The risk mitigation program consists of aCommunication Plan for HCPs, a medication guide for patients andpost-marketing surveillance.

"We are pleased that the FDA has granted approval of Multaq(R) forpatients in a therapeutic area that has seen few new treatment options in thelast twenty years," said Marc Cluzel, MD, Senior Vice President, Research andDevelopment, sanofi-aventis. "Sanofi-aventis' commitment to research anddevelopment in this area is rewarded today, and we hope it will benefit manypatients suffering from this disease."

The incidence of atrial fibrillation is growing worldwide in relation toaging populations. It is emerging as a public health concern and affectsabout 2.5 million people in the United States and 4.5 million people in theEuropean Union. Atrial fibrillation is a potentially life-threateningcondition, with significant burden on patients, health care providers andpayers.

"It is exciting that Multaq(R) will now be available as a treatmentoption for patients with paroxysmal or persistent atrial fibrillation oratrial flutter," said Stuart Connolly, M.D., Professor of Medicine &Director, Division of Cardiology, McMaster University, Hamilton, Canada, andco-principal investigator in the ATHENA study. "Based on clinical studies,Multaq(R) reduces the risk of cardiovascular hospitalizations in patientswith atrial fibrillation / atrial flutter, this outcome could change the waywe approach the management of the disease."

Multaq(R) is to be given twice daily as a 400 mg tablet and should betaken as one tablet with the morning and evening meals. Treatment withMultaq(R) can be initiated in an outpatient setting. Most common adversereactions are diarrhea, nausea, vomiting, abdominal pain, asthenia (weakness)and cutaneous rash.

A registration dossier of Multaq(R) is also under regulatory review bythe European Medicines Agency (EMEA).

About dronedarone (Multaq(R))

Multaq(R), discovered and developed by sanofi-aventis, is one of themajor therapeutic innovations in patients with atrial fibrillation in thelast twenty years.

The efficacy and safety of Multaq(R) 400 mg twice daily was evaluated infive controlled studies, ATHENA, ANDROMEDA, EURIDIS, ADONIS, and DAFNE,involving nearly 6,300 patients including more than 3200 patients whoreceived Multaq(R).

The ATHENA trial, which involved 4,628 patients with AF or AFL and morethan 2,300 patients receiving Multaq(R) on top of standard therapy,demonstrated a 24% reduction in time to first CV hospitalization or all-causemortality (P<0.001) compared with placebo meeting the primary endpoint.

The ANDROMEDA study, was terminated prematurely after enrolment of 627 of1000 planned patients with congestive heart failure, in relation to excessmortality due to worsening heart failure in the dronedarone group [n=25versus 12 (placebo), p=0.027].

The patient population enrolled in the ANDROMEDA and ATHENA studies wassignificantly different. The patients enrolled in ANDROMEDA had relativelysevere heart failure and had been hospitalized, or referred to a specialtyheart failure clinic for worsening symptoms. Patients were predominantly NYHAII and III (New York Heart Association classification) and only 25% had ahistory of AF/AFL at randomization. In contrast, in ATHENA, all patients hada history of AF/AFL, and 71% of patients had no heart failure, 25% were NYHAclass I or II, and only 4% were class III.

The ANDROMEDA and ATHENA trials were published in the New England Journalof Medicine (NEJM) respectively in 2008 and 2009.

Important Safety Information

Multaq(R) is contraindicated in patients with NYHA Class IV heart failureor NYHA Class II-III heart failure with a recent decompensation requiringhospitalization or referral to a specialized heart failure clinic. In aplacebo-controlled study in patients with severe heart failure requiringrecent hospitalization or referral to a specialized heart failure clinic forworsening symptoms (the ANDROMEDA study), patients given dronedarone had agreater than two-fold increase in mortality. Such patients should not begiven dronedarone.

Multaq(R) is also contraindicated in second- or third-degreeatrioventricular (AV) block or sick sinus syndrome (except when used inconjunction with a functioning pacemaker), bradycardia <50 bpm, QTc Bazettinterval greater than or equal to 500 ms and severe hepatic impairment.

Multaq(R) should not be given to patients who are or may become pregnant(Category X) or nursing.

Multaq(R) should not be coadministered with strong CYP 3A inhibitors ormedicinal products that prolong the QT interval.

In patients with new or worsening heart failure, the suspension ordiscontinuation of Multaq(R) should be considered.

Serum creatinine levels increase by about 0.1mg/dL following Multaq(R)treatment initiation. The elevation has a rapid onset, reaches a plateauafter 7 days and is reversible after discontinuation.

Hypokalemia and hypomagnesemia may occur with concomitant administrationof potassium-depleting diuretics. Potassium levels should be maintained inthe normal range pre and during administration.

For full prescribing information, please visithttp://products.sanofi-aventis.us/Multaq/Multaq.pdf

About Atrial Fibrillation/Atrial Flutter

Atrial fibrillation is the leading cause of hospitalization forarrhythmia in the U.S. and represents one-third of hospitalizations forarrhythmia in Europe. Hospitalization associated with AF has increaseddramatically (two-to-three fold) in recent years in the U.S. Atrialfibrillation is a complex disease that increases the risk of stroke up tofive-fold, worsens the prognosis of patients with cardiovascular riskfactors, and doubles the risk of mortality. Atrial flutter, another type ofarrhythmia generating in the atrium, occurs less frequently, and may evolveinto atrial fibrillation.

About sanofi-aventis

Sanofi-aventis, a leading global pharmaceutical company, discovers,develops and distributes therapeutic solutions to improve the lives ofeveryone. 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 thePrivate Securities Litigation Reform Act of 1995, as amended. Forward-lookingstatements are statements that are not historical facts. These statementsinclude product development, product potential projections and estimates andtheir 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 similarexpressions. Although sanofi-aventis' management believes that theexpectations reflected in such forward-looking statements are reasonable,investors are cautioned that forward-looking information and statements aresubject to various risks and uncertainties, many of which are difficult topredict and generally beyond the control of sanofi-aventis, that could causeactual results and developments to differ materially from those expressed in,or implied or projected by, the forward-looking information and statements.

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