Summary of Contents

Pipeline Insight: Anti-arrhythmics - Adjunctive Role for Drugs in Hybrid Therapy

Product Code: DMHC1886

Price: $7600

publication Date: 20-00-2003

Overview

Introduction

Despite an estimated 2.5m people suffering from atrial fibrillation (AF) in the US alone, there has been relatively little anti-arrhythmic drug development in the past five years, with only one significant approval, Pfizer's Tikosyn.

Scope

• Review of published available epidemiology data

• Discussion of drawbacks of existing drugs and the unmet needs

• Overview of pipeline compounds by phase and company, with in-depth profiles and forecasts for late stage products

• Review of recent developments in cardiac rhythm devices and catheter ablation procedures for the treatment of AF

Highlights

The anti-arrhythmics drug market is stagnant, with growth of just 0.5% from 2001-02. The main problems with current anti-arrhythmic drug therapy are their pro-arrhythmic and toxic side-effects. For developmental compounds to gain market share from the current genericized treatments, it may be sufficient for them to demonstrate equivalent efficacy but with superior safety profiles.

Despite the fact that Stedicor from Procter & Gamble Pharmaceuticals is the most advanced pipeline anti-arrhythmic in terms of clinical development, Datamonitor believes that Sanofi-Synthelabo's dronedarone has the greatest market potential.

Developmental anti-arrhythmics are being trialed with implantable cardiac rhythm devices. Indeed amiodarone (the current gold-standard anti-arrhythmic drug) is standard adjunctive therapy for implantable cardioverter defibrillators. With dronedarone at least two years away from approval, hybrid therapy will be an area of intense investigation in the near future.

Reasons to Purchase

• Access a comprehensive guide to the current treatment options for AF and the potential impact of late-stage compounds on this underserved market

• Gauge the role that cardiac rhythm devices will play in the future treatment of AF, given the unmet needs with drug therapy in this field.

• Access key opinion leader insight into the roles that both hybrid therapy and catheter ablation will play in the future treatment of AF

DRIVERS AND TRENDS

The main problems of current anti-arrhythmic drug therapy are their pro-arrhythmic and toxic side-effects. For developmental compounds to gain market share from the current genericized treatments, it may be sufficient for them to demonstrate equivalent efficacy but with superior safety profiles.

Despite the fact that Stedicor from Procter & Gamble Pharmaceuticals is the most advanced pipeline anti-arrhythmic in terms of clinical development, Datamonitor believes that Sanofi-Synthelabo's dronedarone has the greatest market potential. However with dronedarone at least two years away from approval, hybrid therapy will be an area of intense investigation in the near future.

There is growing interest in the use of catheter ablation for the treatment of AF, with success rates being reported as high as 80%. However, at time of writing, these procedures are predominantly aimed at paroxysmal AF patients. In addition, there is a relative contraindication for patients with structural heart abnormalities, so it would appear that only the 15-20% of 'lone' AF patients would gain optimum benefit from this procedure.

PATIENT POTENTIAL

Overview of the different types of arrhythmia and ways in which the patient population is segmented. Includes forecasts of the prevalence of atrial fibrillation to 2011.

CURRENT TREATMENT OPTIONS

Review of current treatment options for arrhythmia, including drugs, devices and procedures with a focus on the extent to which these treatments are complementary versus competitive. Importantly, this section identifies the limitations of existing therapy and identifies the unmet needs that make R&D in this area attractive.

R&D APPROACH

Critical analysis of the clinical trial design and clinical endpoints for anti-arrhythmic drugs in standalone and hybrid therapy trials.

ARRHYTHMIA PIPELINE ANALYSIS

Overview of anti-arrhythmic drugs in development in terms of stage of development, company type, region, and formulation (oral or intravenous).

LATE STAGE ANTI-ARRHYTHMIC DRUG ANALYSIS AND FORECASTS

Analysis of clinical trial data, patient potential, marketing factors, strategic analysis of late stage, developmental anti-arrhythmic drugs. Also includes the potential performance of developmental compounds compared to current gold-standard therapy, and revenue forecasts until 2011 for

• Dronedarone

• Stedicor (azimilide)

• Tedisamil

• Tecadenoson

• RSD-1235

OTHER ANTI-ARRHYTHMIC DRUGS IN DEVELOPMENT

Analysis of other compounds in development, where clinical trial data is not sufficient to enable revenue forecasts. Compounds analyzed are

• DTI-0009

• E-047/1

• AZD7009

RECENT DEVELOPMENTS IN DEVICES AND PROCEDURES

Detailed overview and analysis of the recent developments in the treatment of arrhythmia in terms of devices used, and developments within those categories. Devices discussed are:

pacemakers

implantable cardioverter-defibrillators (ICDs)

ablation catheters

OPINION LEADERS INTERVIEWS

Cardiologists interviewed are:

• Dr Steven M. Markowitz

• Dr Richard Sutton

• Dr Mauro Biffi

• Professor Luigi De Ambroggi

DATASETS

Table 1: Prevalence estimates for atrial fibrillation, 2003-11

Table 2: Forecast sales for developmental anti-arrhythmic drugs in the treatment of atrial fibrillation, 2004-11

Table 3: Prevalence estimates for atrial fibrillation, 2003-11

Table 4: Anti-arrhythmic drug effects

Table 5: AFFIRM trial results

Table 6: Global anti-arrhythmic drug sales ($m), 2001(2002

Table 7: Amiodarone: key facts

Table 8: SAFE-T: median time to AF recurrence in days

Table 9: Sotalol: key facts

Table 10: Tikosyn: key facts

Table 11: DIAMOND-MI primary and secondary endpoint results

Table 12: Effect of dofetilide on hospitalization for worsening heart failure

Table 13: Pharmacological cardioversion rates

Table 14: Probability of remaining in sinus rhythm at one year

Table 15: Average direct costs of care for pacemaker and ICD implantation in Canada 1997-1998

Table 16: Novel anti-arrhythmic compounds in development, 2003

Table 17: Drug development by regional company type and phase, 2003

Table 18: Key products in late stage R&D pipeline, 2003

Table 19: EU and US sales forecasts for dronedarone for 2005-11

Table 20: Factors affecting dronedarone revenues, 2005-11

Table 21: ASAP meta-analysis

Table 22: ALIVE: survival and safety of all and high-risk patients

Table 23: EU and US sales forecasts for azimilide, 2004-11

Table 24: Factors affecting azimilide revenues, 2004-11

Table 25: EU and US sales forecasts for tedisamil 2005-11

Table 26: Impacting factors on the revenues of tedisamil, 2005-11

Table 27: TEMPEST trial results

Table 28: EU and US sales forecasts for tecadenoson, 2007-11

Table 29: Factors affecting the revenues of tecadenoson to 2011

Table 30: CRAFT trial results

Table 31: EU and US sales forecasts for RSD-1235, 2007-11

Table 32: Factors affecting the revenues of RSD-1235, 2003-2011

Table 33: Forecast sales for developmental anti-arrhythmic drugs in the treatment of atrial fibrillation, 2004-11

Table 34: Other developmental anti-arrhythmics, 2003

Table 35: Leading global cardiac rhythm manufacturers

Table 36: Incidence of AF and new AF with dual chamber and single chamber pacing

Table 37: Dual chamber versus single chamber pacing, multi-variable analyses

Table 38: UKPACE: all-cause mortality to five years

Table 39: UKPACE: risk of stroke/TIA/thromboembolism

Table 40: UKPACE: risk of AF at three years

Table 41: ADOPT-A trial results

Table 42: AVID trial prospective cost analysis

Table 43: AMIOVIRT: trial results

Table 44: DAVID trial results

Table 45: Leading catheter ablation manufacturers

Table 46: Multivariate predictors of death after AV node ablation and pacemaker implantation

Table 47: Pain differences in cryoablation and RF ablation

Table 48: FROSTY trial results

Table 49: Dr Markowitz: unmet needs in arrhythmia

Table 50: Dr Markowitz: clinical trial design criteria in arrhythmia

Table 51: Dr Markowitz: late stage developmental anti-arrhythmics

Table 52: Dr Sutton: unmet needs in arrhythmia

Table 53: Dr Sutton: clinical trial design criteria in arrhythmia

Table 54: Dr Sutton: late stage developmental anti-arrhythmics

Table 55: Dr Biffi: unmet needs in arrhythmia

Table 56: Dr Biffi: clinical trial design criteria in arrhythmia

Table 57: Dr Biffi: late stage developmental anti-arrhythmics

Table 58: Prof de Ambroggi: unmet needs in arrhythmia

Table 59: Prof de Ambroggi: clinical trial design criteria in arrhythmia

Table 60: Prof de Ambroggi: late stage developmental anti-arrhythmics

Table 61: Developmental anti-arrhythmics compared to amiodarone

Table 62: Estimated penetration rates and costs for developmental anti-arrhythmics in Europe

Table 63: Estimated penetration rates and costs for developmental anti-arrhythmics in the US

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