Pipeline Insight: Antiarrhythmics - RSD1235 In A Class Of Its Own

Published by: Datamonitor

Published: May. 17, 2006 - 160 Pages

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

CHAPTER 1 ADDENDUM

Background

How will this delay affect antiarrhythmic forecasts moving forward?

Assumptions for updated forecasts

Previous market and pipeline forecasts for the antiarrhythmics market (dated May 17, 2006)

Updated market and pipeline forecasts for the antiarrhythmics market (dated June 23, 2006)

Implications of the delayed launch of RSD1235 (intravenous formulation)

Market forecasts and key events

Summary

CHAPTER 2 EXECUTIVE SUMMARY

Scope of the analysis

Historical perspective of the antiarrhythmics market

Size of the antiarrhythmics market in 2005

Datamonitor insight into the antiarrhythmic market

At the end of 2005, sales within the antiarrhythmics drug market were in decline. With the main problems of current antiarrhythmic drug therapy surrounding their pro-arrhythmic and toxic side effects, it may be sufficient for developmental compounds to demonstrate equivalent efficacy but superior safety profiles to gain market share from the current genericized treatments.

By 2015 the global antiarrhythmic market will be worth $3.5 billion, with sales of pipeline products accounting for over two thirds of the market by this time. Cardiome's RSD1235 (intravenous formulation) is predicted to command 27% of the whole market by 2015 on the back of good safety and efficacy data, combined with the involvement of Japanese pharmaceutical giant, Astellas, in the sales and marketing of the product in the US.

Of the orally active antiarrhythmics currently vying for amiodarone's crown, P&G Pharmaceuticals' Stedicor (azimilide) looks set to win the battle with Sanofi-Aventis' next generation antiarrhythmic Multaq (dronedarone), due to a combination of robust late-stage clinical trial data for Stedicor, particularly from the SHIELD (Shock Inhibition Evaluation with Azimilide) study, and lingering concerns over the relative safety of Multaq.

Summary

Key metrics

CHAPTER 3 PATIENT POTENTIAL

Normal heart electrical activity

What do we mean by the term arrhythmia?

Bradycardia

Tachycardia

Supraventricular tachycardias (SVTs)

Ventricular tachycardias

Other arrhythmias originating in the atria

Premature supraventricular contraction or premature atrial contraction (PAC)

Other arrhythmias originating in the ventricle

Premature ventricular contraction (PVC)

Pathophysiology of cardiac arrhythmia

Normal cardiac electrical activity vs irregularity

Non-nodal/fast response action potentials

Nodal/pacemaker action potentials

Epidemiology of atrial fibrillation

Future trends in the incidence and prevalence of AF

Methodology

Unmet needs in arrhythmia

Decreased mortality

Improved safety

Improved quality of life (QoL)

Improved treatment options for patients with underlying co-morbid conditions

Other unmet needs

The ideal anti-AF drug!

CHAPTER 4 PIPELINE OVERVIEW

Pipeline overview

Breakdown by development stage

Breakdown by company

Breakdown by mechanism

CHAPTER 5 R&D APPROACH

Principles of antiarrhythmic pharmacotherapy

Classification of current antiarrhythmics

Class I antiarrhythmics

Class II antiarrhythmics

Class III antiarrhythmics

Class IV antiarrhythmics

Classification of pipeline products

Novel targets for the treatment of cardiac arrhythmias

Potassium channel blockers

Sodium channel blockers

Adenosine A1 receptor agonists

Clinical trial design in arrhythmia

Comparator therapy

There is no single gold standard therapy

Chronic trials

In-hospital trials

Clinical trial endpoints in arrhythmia

Mortality rates

Efficacy

Chronic trials

In-hospital trials

Safety data

Cost efficacy

Patient numbers

Chronic trials

In-hospital trials

Trial length

Starting points

Patient selection

Hybrid therapy trials

CHAPTER 6 CLASS III ORAL ANTIARRHYTHMICS LATE-STAGE DRUG ANALYSIS & FORECASTS

Definition of current comparator therapies

Cordarone (amiodarone)

Indications

Side effects

Amiodarone's efficacy

Conclusion

Multaq (dronedarone; SR-33589)

Drug overview

Clinical trial data

Datamonitor comments

Patient potential

Marketing factors

SWOT analysis of dronedarone

Performance against benchmark criteria

Forecasts to 2015

Stedicor (azimilide)

Drug overview

Clinical trial data

ASAP

ALIVE

SHIELD

Ongoing Trials

A-STAR (Azimilide supraventricular Tachyarrhythmia reduction)

A-COMET I and II (The azimilide cardioversion maintenance trials)

Patient potential

Azimilide in the ICD population

Azimilide in the AF population

Marketing factors

SWOT analysis

Performance against benchmark criteria

Forecast to 2015

CHAPTER 7 CLASS III INTRAVENOUS ANTIARRYHTHMIC LATE-STAGE DRUG ANALYSIS & FORECASTS

Definition of current comparator therapies

Corvert (ibutilide)

Conclusion

RSD1235 (intravenous formulation)

Drug overview

Development history

Clinical trial data

Phase I

Phase II

Phase III

Ongoing trials

Patient potential

Marketing Factors

Performance against benchmark criteria

SWOT analysis

Forecast to 2015

Pulzium (tedisamil)

Drug overview

Clinical trial data

Phase I

Phase II

Phase III

Patient potential

Marketing Factors

Performance against benchmark criteria

SWOT analysis: Tedisamil compared to Flecainide

Forecast to 2015

CHAPTER 8 ADENOSINE RECEPTOR AGONIST LATE-STAGE DRUG ANALYSIS & FORECASTS

Definition of current comparator therapies

Adenosine

Tecadenoson (CVT-510)

Drug overview

Clinical trial data

Phase III

Patient potential

Marketing factors

Performance against benchmark criteria

SWOT analysis

Forecast to 2015

CHAPTER 9 OTHER PIPELINE ANTIARRHYTHMICS

Phase II compounds

AVE-0118

Drug overview

Preclinical data

Phase II trials

AZD-7009

Drug overview

Phase I trials

Nibentan

Drug overview

Preclinical data

RSD1235 (oral formulation)

Drug overview

Phase I trials

Phase II trials

Selodenoson IV

Drug overview

Phase II trials

Preclinical data

Phase I trials

SSR-149744

Preclinical studies

Clinical trials

Phase I compounds

AVE-1231

PJ-875

Selodenoson (oral controlled release)

CHAPTER 10 COMPARATIVE ANALYSIS OF ANTIARRHYTHMIC PIPELINE

Comparative forecasts

Comparative analysis

APPENDIX A

Methodology

Datamonitor forecast methodology.

Epidemiology forecasts

Product forecasts

Datamonitor drug assessment summary

Contributing experts

References

Report methodology

APPENDIX B

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare's therapy area capabilities

About the cardiovascular analysis team

Key therapy team members

Dr Allison Fleetwood, Director, Cardiovascular, Diabetes and Women's Health

Dr Duncan Emerton, Senior Analyst, Cardiovascular (report contact)

Disclaimer

List of Tables

Table 1: Previous US and M5EU forecasted sales for antiarrhythmic pipeline products ($m) and total market value, 2007-15

Table 2: Updated US and M5EU forecasted sales for antiarrhythmic pipeline products ($m) and total market value, 2007-15

Table 3: Prevalence estimates for atrial fibrillation, 2005-15

Table 4: US and M5EU forecasted sales for antiarrhythmic pipeline products ($m), 2007-15

Figure 9: Electrocardiogram of a single heartbeat

Table 5: Mechanism of a non-pacemaker cardiac action potential

Table 6: Prevalence estimates for atrial fibrillation, 2005-15

Table 7: The antiarrhythmic R&D pipeline, 2006

Table 8: Distribution of antiarrhythmic drugs by company, 2006

Table 9: Key Class III antiarrhythmic drugs in late-stage development for cardiac arrhythmia, 2006

Table 10: Amiodarone: key facts

Table 11: Results of both AF/AFL and PSVT arms of the four ASAP trials

Table 12: ALIVE: survival and safety of all and high-risk patients

Table 13: Key intravenous, multi-factorial antiarrhythmic drugs in late-stage R&D for cardiac arrhythmia, 2006

Table 14: Conversion of AF to SR in the ACT 1 study

Table 15: Non-cardiac Adverse Events (0- to 24-hour period)

Table 16: Key adenosine receptor agonists in late-stage development for cardiac arrhythmia, 2006

Table 17: TEMPEST: Primary Efficacy Assessment

Table 18: Other developmental antiarrhythmics, 2006

Table 19: US and M5EU forecasted sales for antiarrhythmic pipeline products ($m), 2007-15

Table 20: Research, clinical and commercial attractiveness summary for key late-phase pipeline antiarrhythmic products

Table 21: Datamonitor drug assessment parameters

List of Figures

Figure 1: Future expansion of the global antiarrhythmics market will be fueled by five new product launches between 2007 and 2010

Figure 2: Impacts on the global antiarrhythmic market, 2006-2015

Figure 3: The global antiarrhythmics market 2005 by volume (SU) and sales ($)

Figure 4: Future expansion of the global antiarrhythmics market will be fueled by five new product launches between 2007 and 2010

Figure 5: Impacts on the global antiarrhythmic market, 2006-2015

Figure 6: Electrical activity of the heart-yellow coloring indicates the electrical path

Figure 7: The relationship between electrical and mechanical events in the cardiac cycle

Figure 8: Segmentation and inter-relationships of the main types of arrhythmia

Figure 10: Schematic diagram of an action potential generated by a non-nodal e.g. ventricular muscle cell

Figure 11: Key unmet needs in the treatment of arrhythmia, 2006

Figure 12: 2002 guidelines for management of AF in patients with concomitant heart disease

Figure 13: Pipeline overview of antiarrhythmic drugs, 2006

Figure 14: Distribution by each phase of development , 2006

Figure 15: Sanofi-Aventis is developing over a quarter of the pipeline products, 2006

Figure 16: Breakdown of antiarrhythmic pipeline by mode of action, 2006

Figure 17: The fast-response action potential

Figure 18: A ventricular action potential and the effect of Class I drugs

Figure 19: Global sales decline of the antiarrhythmics market, 2002-05

Figure 20: DAFNE trial design

Figure 21: SWOT analysis of dronedarone

Figure 22: Assessment of dronedarone's performance indicators compared to amiodarone

Figure 23: US and M5EU sales forecast for Multaq ($m), 2007-15.

Figure 24: SVA4 - a typical ASAP trial design

Figure 25: ALIVE trial design

Figure 26: SWOT analysis of Stedicor

Figure 27: Assessment of azimilide's performance indicators

Figure 28: US and M5EU sales forecast for Stedicor ($m), 2007-15

Figure 29: CRAFT trial design

Figure 30: Assessment of RSD1235's performance indicators compared to Ibutilide

Figure 31: SWOT analysis of RSD1235

Figure 32: Sales forecast for RSD1235 IV in the US and EU markets, 2007-15

Figure 33: IV tedisamil trial design

Figure 34: Assessment of Tedisamil's performance indicators compared to Flecainide

Figure 35: Tedisamil SWOT analysis

Figure 36: Sales forecast for Tedisamil in the US and EU markets, 2009-15

Figure 37: TEMPEST trial design

Figure 38: Assessment of Tecadenoson performance indicators compared to adenosine

Figure 39: SWOT analysis of tecadenoson

Figure 40: Sales forecast for Tecadenoson in the US and EU markets, 2010-15

Figure 41: Research, clinical and commercial attractiveness summary for key late-stage antihypertensive pipeline products

Figure 42: Research, clinical and commercial attractiveness summary for key late-stage antiarrhythmic products

Figure 43: Example of Datamonitor drug assessment scorecard

Figure 44: Example of Datamonitor drug assessment graph

Abstract

Datamonitor believes that RSD1235 (iv) has the potential to have a significant impact on the treatment of atrial fibrillation. In addition, P&G's Stedicor and Sanofi-Aventis' Multaq also offer advances on current treatments, with improvements in efficacy and safety therein.

• Evaluation of patient potential for developmental antiarrhythmics over the period 2006-2015
• Scrutiny of key impacts on the R&D approach and cost, evaluation of optimal clinical trial end points and identification of suitable comparators
• Evaluation of key players in the arrhthymics market and opposing company approaches to development and commercialization
• Analysis of key antiarrhymic drugs in development and their ability to satisfy major unmet needs and compete with existing agents

2005 saw sales in the antiarrhythmics drug market decline. With key problems of current antiarrhythmic drug therapy surrounding their pro-arrhythmic and toxic side effects, it may be sufficient for developmental compounds to demonstrate equivalent efficacy but superior safety profiles to gain market share from the current genericized treatments.

By 2015 the global antiarrhythmic market will be worth $3.5 billion, with sales of pipeline products accounting for over two thirds of the market by this time. RSD1235 (iv) is predicted to command 27% of the whole market by 2015 on the back of good trial data and the involvement of Astellas in the promotion of the product in the US.

P&G Pharma's Stedicor (azimilide) looks set to become the most successful orally active antiarrhythmic due to a combination of robust late-stage clinical trial data for Stedicor, particularly from the SHIELD (Shock Inhibition Evaluation with Azimilide) study, and lingering concerns over the relative safety of Sanofi-Aventis' Multaq (dronedarone).

• Explore physician attitudes to the newer antiarrhythmic drugs, and the threats faced by existing and developmental products
• Predict future market leaders using our independent sales forecasts for products in late stage development in both existing and novel classes
• Identify early stage antiarrhythmic compounds with high potential being developed by companies seeking a marketing partner

About MarketResearch.com
MarketResearch.com is an online aggregator selling over 160,000 market research reports, company profiles and country profiles from over 600 research firms. Our reports will provide you with the critical business and competitive intelligence you need for strategic planning and marketing research. Coverage includes the US, UK, Europe, Asia and global markets.