Market Report Source

Overview

Introduction

The total asthma and COPD population in 2006 is estimated to be 44.8 million and 28.8 million respectively. While the majority of patients are well controlled with current therapies, the remaining unmet needs are twofold: first, to find better options for the 1.7 million patients with severe asthma; second, to identify effective anti-inflammatory drugs in COPD.

Scope

*Discussion and quantification of the patient potential and segmentation in both Asthma and COPD *Detailed overview and assessment of drugs in mid-to late stage clinical development, highlighting recent clinical trial results *Assessment of the remaining unmet clinical needs in both asthma and COPD, analyzing the potential of new targeted therapies *Ten year indication-based sales forecast to 2015 for major Phase III to recently launched drugs

Highlights

Global asthma/COPD sales are forecast to grow to $30 billion by 2015, with ICS/LABA combinations set to retain their leading position by value, followed by anticholinergics. The ICS/LABA class was long dominated by GlaxoSmithKline’s Advair/Seretide but will see dramatically increased competition in the future with several new product launches.

Despite many years and billions of dollars spent on finding drugs that slow or reverse disease progression in COPD, progress remains elusive. Several drugs that were initially hailed as breakthroughs have failed to live up to their initial promise, but conservative drug regulators and badly chosen clinical endpoints may have to share the blame.

Targeted therapies offer new hope for severe asthma sufferers. Despite several setbacks over the past years, the research pipeline remains full. Although it is still difficult to predict which approach may work for whom, Amgen/Wyeth’s anti-TNF alpha therapy Enbrel is thought to be the next biological drug to be launched in asthma.

Reasons to Purchase

*Identify the remaining opportunities in the Asthma and COPD market place and possible licensing partners *Learn about new biological targeted therapy approaches, shifting R&D approaches and changing clinical trial endpoints *Evaluate forecasts of the asthma/COPD market to 2015, and predict the performance of key drugs

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Infectious Disease and Respiratory pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Contributing experts

Datamonitor insight into the asthma/COPD market

CHAPTER 2 PATIENT POTENTIAL

Definition and etiology of asthma

Segmentation of asthma

Childhood asthma

Adult asthma

Refractory asthma

Epidemiology of asthma

Unmet needs in asthma

Lack of disease control in patients with refractory asthma

Lack of compliance and disease understanding

Side effects

Lack of cure

The allergic march

Definition and etiology of COPD

Segmentation of COPD

Epidemiology of COPD

Unmet needs in COPD

Lack of cure/halt to disease progression

Difficult to suppress inflammation

Poor management of exacerbations

Low awareness and diagnosis

CHAPTER 3 R&D APPROACH

Classification of asthma/COPD pipeline products

Bronchodilators

Anti-inflammatories

ICS/LABA combinations

Biologicals

Clinical trial design in asthma/COPD

Comparing to gold standard

Combination products

Life-cycle management (LCM) strategies

Clinical trial endpoints in asthma/COPD

FEV1 remains most frequently used endpoint

FDA recognizes need for new endpoints

Exacerbations become increasingly significant target

Mortality endpoint can differentiate treatments in COPD

Clinical outcomes versus markers

CHAPTER 4 ASTHMA/COPD PIPELINE ANALYSIS

Key companies involved in the asthma/COPD pipeline

GlaxoSmithKline (GSK)

AstraZeneca (AZ)

Boehringer-Ingelheim (BI)

Merck & Co (Merck)

Novartis/Schering-Plough

Strategies for success

CHAPTER 5 FIXED DOSE ICS/LABA COMBINATIONS ANALYSIS & FORECASTS

Definition of current comparator therapy

Gold standard Advair/Seretide is threatened from several sides

Symbicort’s US approval will boost sales

Super Advair unable to repeat Advair’s success

Clinical trial data

Symbicort SMART indication differentiates it from Advair

Clinical trial data

Foster – similar efficacy at half the price?

Clinical trial data

Alvesco combo – potentially best ICS/LABA combination held back by trial delays

Clinical trial data

Mometasone/formoterol and mometasone/indacaterol

Flutiform will need to compete on price

CHAPTER 6 INHALED CORTICOSTEROIDS ANALYSIS AND FORECAST

Definition of current comparator therapy

Alvesco’s development fraught with uncertainties and setbacks

Clinical trial data

Asmanex too late to have a big impact

CHAPTER 7 NOVEL ANTI-INFLAMMATORIES ANALYSIS AND FORECASTS

Definition of current comparator therapy

Targeting the leukotriene cascade

5-LO – Zileuton CR no competition for Singulair

cPLA2-antagonists are promising target

Chemokine inhibitors are a mixed group

CCR antagonists

CXCR antagonists

VLA-4 antagonists – many development failures

PDEIV inhibitors only promising in COPD?

Daxas

Other PDEIV inhibitors

Inhaled immunostimulatory DNA (ISS)

Targeting oligonucleotides

Other novel anti-inflammatories

CHAPTER 8 BIOLOGICALS ANALYSIS AND FORECASTS

Anti-IgE – Xolair to remains unchallenged

Anti-TNF-?

Promising in severe asthma…

...disappointing in COPD

Anti-IL-13

Anti-IL-5

Anti-IL-2

Other monoclonal antibodies targeting cytokines

CHAPTER 9 BRONCHODILATORS ANALYSIS AND FORECASTS

Competition for Spiriva on the horizon

Definition of current comparator therapy

LAS 34273

NVA 237

233705

Long-acting beta2-agonists will be once-daily

Definition of current comparator therapy

GSK’s once-daily LABAs 159797 and 542444

Indacaterol (QAB-149)

Clinical trial data

CHF-4226

Brovana

LABA/LAMA combination products have blockbuster potential in COPD

The SABA CFC-HFA switch in the US

Xopenex HFA

APPENDIX A

Methodology

Datamonitor forecast methodology

Bibliography

Epidemiology

Disease background

Clinical trial data

Press Releases

APPENDIX B

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare’s therapy area capabilities

About the Infectious Disease and Respiratory analysis team

Disclaimer

List of Tables

Table 1: Asthma prevalence and diagnosed population by country and age, 2006

Table 2: COPD prevalence by country and severity among adults over 45 years old, 2006

Table 3: Outcome measures for COPD

Table 4: Overview of asthma/COPD drug development pipeline, 2006

Table 5: GSK’s marketed respiratory portfolio, 2005

Table 6: AstraZeneca’s marketed respiratory portfolio, 2005

Table 7: Boehringer-Ingelheim’s marketed respiratory portfolio, 2005

Table 8: Key marketed and late-stage products for ICS/LABA combinations, 2006

Table 9: ICS/LABA combinations sales in the six major markets ($m), 2005-2015

Table 10: GSK is performing one study with 159797 and two with 642444

Table 11: Studies presented at the ERS Conference in September 2006 regarding Symbicort SMART

Table 12: Key marketed and late-stage products for inhaled corticosteroids, 2006

Table 13: ICS sales in the six major markets ($m), 2005-2015, $millions

Table 14: Key marketed and late-stage products for novel anti-inflammatories, 2006

Table 15: Key marketed and late-stage products for compounds affecting the leukotriene cascade, 2006

Table 16: Key products for CXCR2 agonists, 2006

Table 17: Key marketed and late-stage products for PDEIV inhibitors, 2006

Table 18: Key marketed and late-stage products for biologicals, 2006

Table 19: Key marketed and late-stage products for anticholinergics, 2006

Table 20: Long-acting anticholinergics sales in the six major markets ($m), 2005-2015

Table 21: Key marketed and late-stage products for LABAs, 2006

Table 22: Long-acting beta2-agonists sales in the six major markets ($m), 2005-2015

Table 23: GSK pool of LABA candidates in Phase II trials, 2006

List of Figures

Figure 1: Basic etiology of asthma

Figure 2: Classification of asthma by clinical, pretreatment features

Figure 3: Prevalence of asthma according to classification of severity

Figure 4: Key unmet needs in asthma, 2006

Figure 5: The allergic march is influences by several factors

Figure 6: Rate of decline of FEV1 with age in COPD patients

Figure 7: The inflammation associated with COPD involves neutrophils and alveolar macrophages

Figure 8: Classification of COPD as measured by airflow limitation

Figure 9: Prevalence of COPD at diagnosis according to classification of severity

Figure 10: Key unmet needs in COPD

Figure 11: Overview of asthma and COPD treatments, 2006

Figure 12: Appropriate LCM strategy depends on time and financial investment

Figure 13: Overview of forecasted asthma/COPD drugs in the pipeline, 2006

Figure 14: Key players in the asthma/CODP market, 2005

Figure 15: Pulmicort: a combination of strategies

Figure 16: GSK and AZ continue to develop their ICS/LABA combination products

Figure 17: Sepracor takes advantage of CFC-HFA switch in the US in 2008

Figure 18: ICS/LABA combinations sales in the six major markets ($m), 2005-2015

Figure 19: Warning in Advair prescribing information regarding salmeterol

Figure 20: Advair/Seretide and Symbicort sales in the six major markets, 2001-05

Figure 21: Formoterol is preferred LABA due to short onset of action, long duration and limited side effects

Figure 22: Characteristics of ICS/LABA drugs on the market and in development

Figure 23: ICS/LABA combination sales in the six major markets, 2005-15

Figure 24: Symbicort adjustable maintenance dosing

Figure 25: SMILE study design

Figure 26: ICS/LABA combinations sales in the six major markets, 2005-2015

Figure 27: Study design of two studies

Figure 28: Foster versus Advair/Seretide and Foster versus Symbicort, PEF

Figure 29: ICS/LABA combinations sales in the five major European markets, 2005-2015

Figure 30: ICS/LABA combinations sales in the six major markets, 2005-2015

Figure 31: Mometasone/indacaterol combination shows most promise for Novartis and Schering-Plough

Figure 32: ICS/LABA combinations sales in the six major markets, 2005-2015

Figure 33: ICS/LABA combinations sales in the six major markets, 2005-2015

Figure 34: ICS sales in the six major markets, 2005-2015

Figure 35: Study design and primary endpoint of ciclesonide 160µg versus 640µg

Figure 36: ICS sales in the six major markets, 2005-2015

Figure 37: ICS sales in the six major markets ($m), 2005-2015

Figure 38: Novel anti-inflammatory market is moving towards targeted therapy

Figure 39: Blockbuster potential of anti-inflammatories in COPD is uncertain, 2006-2020

Figure 40: Effect of tipelukast on inflammation cascade

Figure 41: Zileuton affects inflammatory cascade earlier than montelukast

Figure 42: Patient potential breakdown for Zileuton CR in the US

Figure 43: Singulair and Zileuton CR sales in the US ($m), 2005-2015

Figure 44: Efipladib affects inflammatory cascade earlier than montelukast and zileuton

Figure 45: Results from roflumilast RECORD and RATIO studies

Figure 46: Xolair sales in the six major markets, 2005-2015

Figure 47: Long-acting anticholinergics sales in the six major markets, 2005-2015

Figure 48: Respimat SMI demonstrates better lung deposition compared with conventional MDIs

Figure 49: The battle to be second to the once-daily LAMA market is between Almirall, Novartis and GSK

Figure 50: Long-acting anticholinergics sales in the six major markets, 2005-2015

Figure 51: Long-acting beta2-agonists sales in the six major markets ($m), 2005-2015

Figure 52: Long-acting beta2-agonists sales in the six major markets ($m), 2005-2015

Figure 53: Mean serum potassium over time

Figure 54: Patient potential breakdown for arformoterol in the US, 2006

Figure 55: Brovana sales in the US, 2005-2015

Figure 56: LABA/LAMA peak sales in the six major markets

Figure 57: Three possible LABA/LAMA combination drugs in development

Figure 58: The (levo)salbutamol market according to type of delivery device, 2005

Figure 59: The volume and sales values of the (levo)salbutamol market according to type of delivery device, 2005

Figure 60: Xopenex sales in the US, 2005-2015