ESC 2005 - First patient study demonstrates efficacy and safety of AZD7009

In the three highest dose groups, 78% of patients (7/9) with an episode of AF/AFl (atrial flutter) of less than one week at baseline converted to sinus rhythm, whilst 46% (12/26) with an episode of AF/AFl of greater than one week duration also converted.

The study also demonstrated that AZD7009 iv is generally well tolerated.¹ Since some pharmacological treatments for AF/AFl are potentially proarrhythmic (have the tendency to cause other arrhythmias), ² the safety of AZD7009 was carefully monitored. AZD7009 is a novel antiarrhythmic, acting through mixed potassium and sodium channel blockade, which has a potent effect on the atria and a low risk of proarrhythmias. There were no cases of the serious arrhythmia Torsades de Pointes according to pre-defined criteria.¹ Today’s data is an important step in the investigation of AZD7009 iv as a possible antiarrhythmic treatment for the future, but further large-scale studies are required in order to fully understand and test its potential.

“Today’s early clinical data are encouraging, and indicate that AZD7009 is safe and effective in restoring sinus rhythm in both short and longer term AF episodes, and we welcome these results and look forward to investigating the findings further,” comments Professor Harry Crijns, lead investigator of the study.

Current approaches to terminate AF by restoring sinus rhythm (cardioversion) include pharmacological treatments, direct current (DC) cardioversion or surgical procedures. Currently available pharmacological treatments are limited either by their modest efficacy or by potentially serious side effects, whilst DC cardioversion can be unpleasant for the patient and requires anaesthesia. The Euro Heart Survey on atrial fibrillation, conducted in 35 countries to assess the management of AF and also presented at the ESC congress, has concluded that there is an unmet need for new, safe and effective antiarrhythmic drugs to treat short and longer term AF.³

Further enquiries to:

For further updates, news and information please visit http://www.astrazenecapressoffice.com or contact:

Andrew Thomas, Cohn & Wolfe
Tel: +44 7803 585254 (onsite at ESC)
Email: andrew_thomas@uk.cohnwolfe.com

Or

Patricia O’Connor, Global PR Manager (Atrial Fibrillation), AstraZeneca
Tel: +46 708 46 76 33 (onsite at ESC)
E-mail: patricia.o'connor@astrazeneca.com





AZD7009
AZD7009 is an antiarrhythmic drug in early clinical development for the treatment of AF. Preclinical studies have shown that AZD7009 is a promising drug for converting AF to sinus rhythm. Early clinical studies support preclinical findings and show that AZD7009 is well tolerated overall.

About the Study
‘Safety and efficacy of AZD7009 given intravenously to patients for conversion of atrial fibrillation / atrial flutter’, Crijns, H et al, is a Phase II, double-blind, placebo controlled study and the first undertaken with AZD7009 in AF patients. The aims of the study were to examine the safety and efficacy of AZD7009 across a range of concentrations.

A total of 122 patients with AF or atrial flutter which had lasted for between 48 hours and 90 days were randomised to receive either one of seven concentrations (doses) of AZD7009 as an infusion, or placebo. The drug was given as a 30-minute bolus followed by a 150-minute infusion (total treatment period three hours).

Atrial Fibrillation
Atrial fibrillation (AF) is a type of arrhythmia (irregular heart rhythm), which is characterised by the ‘quivering’ or rapid contraction of the atria (upper chambers of the heart). The symptoms of AF include palpitations, dizziness, fainting, tiredness, weakness, shortage of breath and angina. AF can have serious consequences and significantly increases the risk of death from stroke, heart attack or heart failure.³

Current Treatment Options
Current treatment approaches for AF involve one of the following, plus anticoagulant therapy:

• Rhythm control: Aims to convert AF to sinus rhythm (cardioversion) and subsequently to maintain sinus rhythm
• Rate control: Aims to control the frequency of ventricular contractions. Although the heart rate is controlled, sinus rhythm is not restored, and the heart therefore remains in AF and at risk of progressive damage

There are several antiarrhythmic treatments available for pharmacological cardioversion. These are most often administered intravenously and have modest conversion rates influenced by the duration of the current atrial fibrillation episode, so they are less effective than DC cardioversion.² These treatments are not suitable for all patients, and can be associated with potentially serious side effects.² DC cardioversion is commonly used and is successful in most patients, but AF often reoccurs, necessitating further procedures. It can be unpleasant for patients, requiring sedation or anaesthesia.

AstraZeneca
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world’s leading pharmaceutical companies with healthcare sales of over $21.4 billion and leading positions in sales of gastrointestinal, oncology, cardiovascular, neuroscience and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index. AstraZeneca has more than 40 years experience in cardiovascular medicine and aims to increase lifespan and improve quality of life by reducing the risk, prevalence and impact of cardiovascular disease. AstraZeneca has a comprehensive cardiovascular portfolio including CRESTOR^TM_, EXANTA^TM , ATACAND^TM , ZESTRIL^TM , TENORMIN^TM , SELOKEN ZOK /TOPROL-XL^TM and PLENDIL^TM .

References:

References

1. Crijns H et al. Safety and efficacy of AZD7009 given intravenously to patients for conversion of atrial fibrillation / atrial flutter. European Society of Cardiology Congress 2005 (session 3026)
2. Fuster V et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22: 1852–923
3. Crijns H et al. Insights into the management of atrial fibrillation in clinical practice in Europe - results of the Euro Heart Survey on Atrial Fibrillation. European Society of Cardiology Congress 2005 (session 1923)