Market Report Source

Overview

Introduction
Detailed analysis of the Asthma and COPD market. 10 year sales forecast for all major drugs brands in these indications, taking into account new treatment trends, clinical trial data, patent expirations and key new product launches in the 7 major markets.

Scope of this report

• Indication based forecasts for asthma/COPD products and significant pipeline drugs
• Assessment of country-specific drivers and resistors likely to impact the market
• Future market outlook for individual products taking into account key market events, in particular patent expiry and competitor launch dates
• Market overview by geographical area, with value analysis of clinical and commercial factors underlying product performance

Research and analysis highlights
Asthma/COPD sales in the seven major markets are expected to grow to over $24 billion annually by 2010 and drop slightly thereafter due to patent expiries of key products. The ICS/LABA class is set to remain the leading class by value throughout, while the LAMA market will experience the strongest growth, particularly in COPD.

A once-daily LABA/LAMA product should become the top-selling single brand in the seven major markets in 2016, depending on which company launches such a combination product first. However, combined sales of the Advair franchise (Advair/Seretide and once-daily Beyond Advair) will dominate the asthma/COPD market over the next ten years.

The phase-out of CFC-containing inhalers in the US after 2008 will have a big impact on the market for short-acting beta2-agonists (SABAs), increasing this class’ size significantly. The main beneficiary is expected to be IVAX’s (now Teva) ProAir due to its favourable price compared with other marketed HFA SABAs.

Key reasons to read this report

• Identify key opportunities and threats that will impact the use and uptake of new and existing products
• Quantify the future size and scope of the asthma/COPD market and predict the future performance of key compounds
• Understand and capitalize on clinical unmet needs in the market, either through lifecycle management of marketed drugs or new product development

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the respiratory pharmaceutical analysis team CHAPTER 1 EXECUTIVE SUMMARY Objective of the analysis Datamonitor insight into the asthma/COPD market

Contributing experts

Related reports CHAPTER 2 MARKET DEFINITION AND OVERVIEW Market definition for this report Indication sales split Current market situation Strategic scoping and focus CHAPTER 3 COUNTRY MARKET ASSESSMENTS Summary of environmental issues affecting the asthma/COPD market Opportunities and threats in the seven major markets Opportunities Off-label prescribing is popular in the pediatric asthma market EMEA harmonizes drug approval process Smaller companies helped by European regulators

Threats

Governments try to stop increasing healthcare expenditure by controlling pricing and reimbursement Parallel trading threatens return on investment Asthma and COPD prevalence will remain stable Non-compliance is particularly common in asthma Difficulty in conducting clinical trials in COPD US: opportunities and threats Asthma/COPD market overview Opportunities New asthma clinical trial endpoints open doors The CFC-HFA switch will lead to a branded salbutamol market FDA initiatives to decrease product development times US is the only country to allow direct-to-consumer (DTC) advertising of prescription medicines Threats Reimbursement controls are important in decreasing healthcare expenditure in the US Implementation of Medicare Part D influences US healthcare market Parallel trading could increase due to Medicare D’s ‘donut hole’ Prescription Drug User Fee Act (PDUFA) likely to increase fees Reimbursement of nebulized beta2-agonists in COPD are under pressure Japan: opportunities and threats Asthma/COPD market overview Opportunities Characteristics of Japanese society impact the COPD market in particular Separation of manufacturing and marketing entities benefits both Japanese and foreign companies

Japan shows initiatives to open their market

Threats Price cuts still dominate pricing and reimbursement in Japan Increasing uptake of generics Lengthy approval process slows down access to the Japanese market COPD remains underdiagnosed and undertreated France: opportunities and threats Asthma/COPD market overview Opportunities Generics use is still relatively low in France Pricing and reimbursement negotiations to be shortened by new agency Threats France increases its pricing and reimbursement efforts Varying formularies influence hospital prescribing Germany: opportunities and threats Asthma/COPD market overview Opportunities Encouraging environment for novel drug development ePharmacy and mail-order drugs legalized Disease management programs encourage patients to be more involved Threats Reimbursement controls are important in decreasing healthcare expenditure in Germany Generic penetration in Germany is relatively high Germany focuses attention on high doses of medicines for elderly patients ICS/LABA combinations under scrutiny Italy: opportunities and threats Asthma/COPD market overview Opportunities Generic drugs play a small role in Italy Reimbursement negotiations are less restrictive Threats Italy increases its pricing and reimbursement efforts

Spain: opportunities and threats

Asthma/COPD market overview Opportunities The pharmaceutical industry implements strategies to reduce parallel exportation Health ministry introduces ‘Spanish national formulary’ Threats The introduction of a new medicines bill increases the focus on cost containment in Spain The profile of generics is being raised in Spain UK: opportunities and threats Asthma/COPD market overview Opportunities The UK offers an attractive market The pricing and reimbursement environment in the UK is relatively non-restrictive Threats The UK enjoys a strong generics market The post-guidance and pre-guidance effects of NICE are a significant concern CHAPTER 4 FORECAST ANALYSIS Key events Inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) combinations Advair/Seretide will lose first position in ICS/LABA class Symbicort US approval and SMART approach will boost sales Foster competes on price New product launches Major clinical trials Additional indications Patent expiries Oral anti-inflammatories Singulair will remain highest selling NSAID but will suffer from generic entry and new competitors New product launches Additional indications Patent expiries Long-acting anticholinergics (LAMAs) BI tries to differentiate Spiriva before the entry of new competitors New product launches Major clinical trials Additional indications Patent expiries Inhaled corticosteroids (ICS) Pulmicort and Flixotide remain the highest-selling ICS products New product launches Additional indications Patent expiries Long-acting beta2-agonists (LABAs) Serevent and Foradil lead the LABA class New product launches Major clinical trials Patent expiries Biologicals Xolair to become blockbuster by 2014 New product launches Additional indications Patent expiries Short-acting beta2-agonists (SABAs) Sepracor’s Xopenex franchise to reach revenues of over $1 billion IVAX/Teva’s ProAir set to make most out of CFC-HFA switch in the US Combivent sales to decline slightly Short-acting anticholinergics (SAMAs) Other asthma and COPD therapies Bronchial thermoplasty Antibiotics

Immunotherapy

Data definitions, limitations and assumptions Standard Units Japanese Market Data Derivation of Sales Forecasts and Pricing Trends Regional launch dates for new products Generic Erosion and Pricing Assumptions The ‘Others’ class

Forecasts

Forecast methodology CHAPTER 5 COMMERCIAL IMPACT AND LIFECYCLE MANAGEMENT: CASE STUDIES The strategies behind combination products Pricing First-to-market advantage Patent protection Combinations are here to stay The impact of the CFC-HFA switch in the US HFA as alternative to CFC 3M’s patents will prevent entry of other HFA SABAs ProAir will be highest-selling SABA after 2009 with peak sales of $650m The increasing importance of inhaler devices in the asthma/COPD market Lack of detailed guidelines and physician skills pMDIs versus DPIs The ideal inhaler The Novolizer and the Respimat SMI The Novolizer – optimal patient feedback and fine particles The Respimat SMI – slow moving mist with deep lung penetration BIBLIOGRAPHY Bibliography APPENDIX A – MARKET DATA AND MAJOR BRAND KEY FACTS Summary asthma/COPD market data ICS/LABA combinations market data ICS/LABA combinations market data Anticholinergics market data Biologicals market data Oral anti-inflammatories market data Beta2-agonists market data Inhaled corticosteroids (ICS) market data APPENDIX B – MARKET FORECAST DATA Market forecast data APPENDIX C Contributing experts Report methodology About Datamonitor

About Datamonitor Healthcare

About the respiratory and infectious disease analysis team Disclaimer List of Tables

Table 1: Prescription of off-label and unlicensed drugs in pediatrics

Table 2: Sales of ICS/LABA combination products in the seven major markets ($m), 2006-2016 Table 3: Price difference between launched ICS/LABA combination products in Germany, 2007 Table 4: Sales of oral anti-inflammatory products in the seven major markets ($m), 2006-2016 Table 5: Sales of long-acting anticholinergic products in the seven major markets ($m), 2006-2016 Table 6: Sales of inhaled corticosteroid products in the seven major markets ($m), 2006-2016 Table 7: Sales of long-acting beta2-agonist products in the seven major markets ($m), 2006-2016 Table 8: GSK pool of LABA candidates in Phase II trials, 2006 Table 9: Sales of monoclonal antibody products in the seven major markets ($m), 2006-2016 Table 10: Sales of short-acting betas2-agonist products in the seven major markets ($m), 2006-2016 Table 11: Sales of short-acting anticholinergic products in the seven major markets ($m), 2006-2016 Table 12: Costs per bronchoscopy Table 13: Launch forecast assumptions used in the asthma/COPD market, 2007 Table 14: Generic erosion in the seven major markets over 3 years (%) Table 15: Generic price discounts in the seven major markets (%) Table 16: Classes rolled up into the ‘Others’ category by country Table 17: Prices of HFA (levo)salbutamol products in 2006 Table 18: US – Summary market data, 2006 and 2016 Table 19: Japan – Summary market data, 2006 and 2016 Table 20: France – Summary market data, 2006 and 2016 Table 21: Germany – Summary market data, 2006 and 2016 Table 22: Italy – Summary market data, 2006 and 2016 Table 23: Spain – Summary market data, 2006 and 2016 Table 24: UK – Summary market data, 2006 and 2016 Table 25: Advair/Seretide: key facts Table 26: Symbicort: key facts Table 27: Foster: key facts Table 28: Spiriva: key facts Table 29: Atrovent: key facts Table 30: Combivent: key facts Table 31: Duoneb: key facts Table 32: Berodual: key facts Table 33: Xolair: key facts Table 34: Singulair: key facts Table 35: Accolate: key facts Table 36: Onon: key facts Table 37: Zyflo: key facts Table 38: Serevent: key facts Table 39: Foradil: key facts Table 40: Ventolin: key facts Table 41: Proventil: key facts Table 42: Xopenex: key facts Table 43: ProAir: key facts Table 44: Pulmicort: key facts Table 45: Flixotide/Flovent: key facts Table 46: Becotide: key facts Table 47: Qvar: key facts Table 48: Beclazone: key facts Table 49: Clenil: key facts Table 50: Azmacort: key facts Table 51: Aerobid: key facts Table 52: Alvesco: key facts Table 53: Asmanex: key facts Table 54: Seven major markets – forecast sales in the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) Table 55: Five major European markets – forecast salesin the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) Table 56: US – forecast sales in the asthma/COPD amrket, 2006-2016 ($m; 2006 figures are actuals) Table 57: Japan – forecast sales in the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) Table 58: France – forecast sales in the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) Table 59: Germany – forecast sales in the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) Table 60: Italy – forecast sales in the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) Table 61: Spain – forecast sales in the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) Table 62: UK – forecast sales in the asthma/COPD market, 2006-2016 ($m; 2006 figures are actuals) List of Figures

Figure 1: Total sales in the seven major markets, by class ($bn), 2002-2006

Figure 2: Asthma/COPD market by class and value in the seven major markets, 2006 Figure 3: Top five brands by sales in seven major markets ($bn), 2006 Figure 4: Respiratory market sales split by country ($m), 2006-2016 Figure 5: Summary of environmental issues affecting the asthma/COPD market, 2007 Figure 6: Healthcare spending as a proportion of GDP in the seven major markets, 2004 Figure 7: Key pricing controls used globally, 2006 Figure 8: Trends in the prevalence of asthma symptoms according to the ISAAC Phase Three study, 2006 Figure 9: Percentage of daily smokers among adult population Figure 10: US sales of asthma/COPD treatments by class ($bn), 2002-2006 Figure 11: Different endpoints show different profile of high versus low dose budesonide Figure 12: Traditional and possible novel endpoints in asthma and COPD trials Figure 13: Decrease of FDA’s mean total approval time, 1995-2005 Figure 14: Japan sales of asthma/COPD treatments by class ($bn), 2002-2006 Figure 15: Increase in life expectancy between 1960 and 2003 across the seven major markets Figure 16: France sales of asthma/COPD treatments by class ($bn), 2002-2006 Figure 17: Germany sales of asthma/COPD treatments by class ($bn), 2002-2006 Figure 18: Italy sales of asthma/COPD treatments by class ($bn), 2002-2006 Figure 19: Spain sales of asthma/COPD treatments by class ($bn), 2002-2006 Figure 20: UK sales of asthma/COPD treatments by class ($bn), 2002-2006 Figure 21: Sales of the ICS/LABA combination class compared to overall asthma/COPD sales in the seven major markets ($bn), 2006-2016 Figure 22: Sales of Advair/Seretide, Symbicort and Foster in the seven major markets ($bn), 2006-2016 Figure 23: Once daily QAB149 is comparable to twice-daily formoterol Figure 24: Sales of Advair/Seretide, Beyond Advair, Advair family and QMF149 in the seven major markets ($bn), 2006-2016 Figure 25: Sales of Alvesco Combo, Flutiform and MFF258 in the seven major markets ($m), 2006-2016 Figure 26: Sales of the oral anti-inflammatories class compared to overall asthma/COPD sales in the seven major markets ($bn), 2006-2016 Figure 27: Sales of Singulair, Onon and Accolate in the seven major markets ($m), 2006-2016 Figure 28: Sales of Zyflo, Zileuton CR and MN-001 in the seven major markets ($m), 2006-2016 Figure 29: Sales of the long-acting anticholinergic class compared to overall asthma/COPD sales in the seven major markets ($bn), 2006-2016 Figure 30: The Respimat Soft Mist Inhaler Figure 31: Sales of Spiriva in the seven major markets ($bn), 2006-2016 Figure 32: Sales of LAS 34273, NVA237 and GSK’s LAMA in the seven major markets ($m), 2006-2016 Figure 33: Sales of QVA149 in the seven major markets ($m), 2006-2016 Figure 34: Sales of the inhaled corticosteroid class compared to overall asthma/COPD sales in the seven major markets ($bn), 2006-2016 Figure 35: Sales of Pulmicort and Flixotide/Flovent in the seven major markets ($m), 2006-2016 Figure 36: Sales of beclometasone-based inhalers in the seven major markets ($m), 2006-2016 Figure 37: Sales of Asmanex and Alvesco in Germany ($m), 2003-2006 Figure 38: Sales of Asmanex and Alvesco in the seven major markets ($m), 2006-2016

Figure 39: Patient potential for a once-daily anti-inflammatory for the treatment of COPD in the seven major markets, 2007

Figure 40: Sales of the long-acting beta2-agonist class compared to overall asthma/COPD sales in the seven major markets ($bn), 2006-2016

Figure 41: Sales of Serevent and Foradil in the seven major markets ($m), 2006-2016 Figure 42: Sales of QAB149, GSK’s LABA and CHF 4226 in the seven major markets ($m), 2006-2016 Figure 43: Trials on safety and efficacy of Brovana and Perforomist, 2007 Figure 44: Sales of Brovana and Perforomist in the seven major markets ($m), 2006-2016 Figure 45: Sales of the biologicals class compared to overall asthma/COPD sales in the seven major markets ($bn), 2006-2016 Figure 46: Patient potential for Xolair in the US, 2007

Figure 47: Patient potential for Xolair in Europe, 2007

Figure 48: Sales of Xolair in the seven major markets ($m), 2006-2016 Figure 49: Patient potential for a once-daily monoclonal antibody for the treatment of severe/refractory asthma in the seven major markets, 2007 Figure 50: Sales of the short-acting beta2-agonist class compared to overall asthma/COPD sales in the seven major markets ($bn), 2006-2016 Figure 51: Sales of Xopenex Nebulized and HFA in the seven major markets ($m), 2006-2016 Figure 52: Sales of Ventolin, Proventil and ProAir in the seven major markets ($m), 2006-2016 Figure 53: Sales of Combivent and Duoneb in the seven major markets ($m), 2006-2016 Figure 54: Sales of Atrovent in the seven major markets ($m), 2006-2016 Figure 55: Possible patient potential for bronchial thermoplasty in the US, 2007 Figure 56: Possible revenues for Asthmatx in the US Figure 57: The roles of viral and bacterial infections in asthma Figure 58: Cannibalization versus expansion strategy Figure 59: Sales of Advair/Seretide versus its components in the US ($bn), 2002-2006 Figure 60: First-year of launch and 2016 sales of marketed and pipeline combination products Figure 61: Generic CFC salbutamol market will revert to branded HFA salbutamol market in the US after December 2008 Figure 62: Overview of the salbutamol and levosalbutamol market, HFA versus other, and the impact of the CFC-HFA switch, 2006-2008 Figure 63: Sales of HFA (levo)salbutamol products, 2006-2016 Figure 64: The Novolizer has the characteristics of an ideal inhaler device Figure 65: Respimat SMI demonstrates better lung deposition compared with conventional MDIs