This patient population corresponds to the patients included in the ATHENA study ¹, the largest study ever performed with an anti-arrhythmic drug in atrial fibrillation and the only study to have ever demonstrated a positive impact on cardiovascular (CV) morbidity and mortality.

In ATHENA, dronedarone reduced the risk of cardiovascular hospitalization or death by a significant 24% vs. placebo on top of standard of care including beta-blockers (p<0.001) with no difference in the rate of serious adverse events (19.9% vs 21.1% respectively; p = 0.31).

The Arrhythmia Alliance welcomed the decision by NICE to recommend approval of dronedarone as a second line treatment option for Atrial Fibrillation (AF) patients, reversing its previous draft guidance.

NICE’s Appraisal Committee recognised that dronedarone can and should occupy a currently vaca(2nt place in the care pathway, and that for a large and growing number of patients it could represent the only treatment option open to them.

Trudie Lobban, CEO of the Atrial Fibrillation Association which is campaigning for dronedarone to be approved said: “For thousands of AF patients this news will give them new hope that they will be able to lead a fulfilled and productive life. NICE’s decision is triumph of common sense and will restore patient and healthcare professionals faith in NICE processes and evidence hearing. They took into account the value of the drug to patients whose lives have been crippled with either the symptoms of AF or the side effects of other treatments.  It is important that symptomatic AF patients have access to specialist consultants who will be aware of the benefits of this new drug.

“I would like to thank all the patients, carers and clinicians who took the time to respond to the earlier Appraisal Consultation Document by NICE which ensured that a review was held and evidence from leading arrhythmia clinicians and AF patients was heard. Without their support many thousands of AF sufferers would be left without hope.”

Professor John Camm, Head of the Department of Cardiac & Vascular Sciences at St George’s, University of London, a Trustee of AFA and President of Arrhythmia Alliance said: “This decision will please many clinicians working in our field. It enables us to have the authority to prescribe dronedarone and gives us an additional treatment for patients who may have run out of options. I want to thank the NICE committee for being so responsive to requests to review all the evidence.”

Multaq® will be commercially available in the UK from Tuesday, March 30, 2010.

Multaq® has a fixed dose regimen of twice daily 400 mg tablets to be taken with morning and evening meals. Treatment with Multaq® does not require a loading dose and can be initiated in an outpatient setting. Most common adverse reactions are diarrhea, nausea, vomiting, abdominal pain, asthenia (weakness) and skin rash.

The European Commission granted marketing authorization for Multaq® in November 2009. Multaq® is indicated in the EU in adult clinically stable patients with a history of, or current non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate. ² The use of Multaq® in unstable patients with NYHA class III and IV heart failure is contraindicated. Because of limited experience in stable patients with recent (1 to 3 months) NYHA class III heart failure or with Left Ventricular Ejection Fraction (LVEF) <35%, the use of Multaq® is not recommended in these patients.

Multaq® is currently available in the U.S., Canada, Switzerland, Germany, Denmark, Ireland, Norway and Finland and is being launched in most European countries in 2010.

The NICE process for Multaq®

• The stakeholder consultation period for this ACD closes on 22 April
• Stakeholder comments submitted to NICE on this ACD will be considered at the Appraisal Committee Meeting on 26 May
• If a Final Appraisal Determination (FAD) is produced following the Appraisal Committee Meeting it would be expected in early July
• If the FAD is not appealed, publication of Final Guidance would be expected sometime between July and September.

1. This new appraisal document is not the final NICE guidance on Multaq®.  A consultation period is ongoing until April 22nd, 2010. The appraisal committee will meet again to consider the evidence on May 26, 2010. After this meeting the Committee will prepare the final appraisal determination (FAD) for Multaq®.

References

1. Hohnloser S.H, Crijns H.J.G.M., van Eickels M, et al. Effect of Dronedarone on Cardiovascular Events in Atrial Fibrillation, N Engl J Med 2009; 360:668-78.
2. European Medicines Agency. European Public Assessment Report.  Doc. Ref.: EMA/625172/2009; EMEA/H/C/1043

In the Summary of Positive Opinion, the CHMP has acknowledged that dronedarone has been shown,  in addition to its rhythm and rate controlling properties, to decrease the risk of atrial fibrillation-related hospitalisations.

The positive opinion from the CHMP needs now to be ratified by the European Commission.

“Sanofi-aventis welcomes the positive CHMP recommendation for the approval of Multaq® in the European Union” said Jean-Pierre Lehner, Chief Medical Officer, sanofi-aventis. “This decision brings new hope to people whose lives are impacted by the potential cardiovascular complications of atrial fibrillation. We do think that Multaq^® will contribute to fulfill significant unmet medical needs for the patients”.

The CHMP positive opinion is based on the submission of a comprehensive clinical data package including seven international, multi-center, randomized clinical trials involving more than 7000 patients and including the landmark ATHENA trial.

The ATHENA trial involved 4,628 patients with Atrial Fibrillation / Atrial Futter or a recent history of these conditions and showed that Multaq^® (dronedarone) in addition to standard therapy, reduced the combined endpoint of cardiovascular hospitalization or death from any cause by 24% (p<0.001) when compared to placebo, meeting the study’s primary endpoint. Reported significant adverse events in the Multaq^® arm included diarrhoea, nausea, bradycardia, QT-interval prolongation and cutaneous rash.

The incidence of atrial fibrillation is growing worldwide in relation to aging populations. It is emerging as a public health concern and affects about 4.5 million people and represents one-third of hospitalizations for arrhythmia in the European Union. Atrial fibrillation leads to potential life-threatening complications. AF increases the risk of stroke up to five-fold , worsens the prognosis of patients with cardiovascular risk factors, and doubles the risk of mortality with significant burden on patients, health care providers and payers.

Multaq® has recently received approval from the U.S. Food and Drug Administration (FDA), Health Canada and Swissmedic (Swiss Health Authority).