Pipeline Insight: Asthma/COPD -Targeted therapies on the horizon

ABOUT DATAMONITOR HEALTHCARE 2
About the Infectious Disease and Respiratory pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 4
Scope of the analysis 4
Contributing experts 5
Datamonitor insight into the asthma/COPD market 5
CHAPTER 2 PATIENT POTENTIAL 13
Definition and etiology of asthma 13
Segmentation of asthma 15
Childhood asthma 16
Adult asthma 17
Refractory asthma 17
Epidemiology of asthma 19
Unmet needs in asthma 21
Lack of disease control in patients with refractory asthma 22
Lack of compliance and disease understanding 23
Side effects 23
Lack of cure 23
The allergic march 23
Definition and etiology of COPD 24
Segmentation of COPD 28
Epidemiology of COPD 28
Unmet needs in COPD 30
Lack of cure/halt to disease progression 31
Difficult to suppress inflammation 32
Poor management of exacerbations 32
Low awareness and diagnosis 33
CHAPTER 3 R&D APPROACH 34
Classification of asthma/COPD pipeline products 35
Bronchodilators 35
Anti-inflammatories 38
ICS/LABA combinations 41
Biologicals 42
Clinical trial design in asthma/COPD 43
Comparing to gold standard 43
Combination products 44
Life-cycle management (LCM) strategies 45
Clinical trial endpoints in asthma/COPD 46
FEV1 remains most frequently used endpoint 46
FDA recognizes need for new endpoints 47
Exacerbations become increasingly significant target 48
Mortality endpoint can differentiate treatments in COPD 49
Clinical outcomes versus markers 50
CHAPTER 4 ASTHMA/COPD PIPELINE ANALYSIS 52
Key companies involved in the asthma/COPD pipeline 55
GlaxoSmithKline (GSK) 56
AstraZeneca (AZ) 58
Boehringer-Ingelheim (BI) 60
Merck & Co (Merck) 62
Novartis/Schering-Plough 63
Strategies for success 64
CHAPTER 5 FIXED DOSE ICS/LABA COMBINATIONS ANALYSIS & FORECASTS 68
Definition of current comparator therapy 70
Gold standard Advair/Seretide is threatened from several sides 70
Symbicort’s US approval will boost sales 73
Super Advair unable to repeat Advair’s success 75
Clinical trial data 78
Symbicort SMART indication differentiates it from Advair 82
Clinical trial data 85
Foster - similar efficacy at half the price? 90
Clinical trial data 92
Alvesco combo - potentially best ICS/LABA combination held back by trial delays 96
Clinical trial data 97
Mometasone/formoterol and mometasone/indacaterol 99
Flutiform will need to compete on price 100
CHAPTER 6 INHALED CORTICOSTEROIDS ANALYSIS AND FORECAST 103
Definition of current comparator therapy 105
Alvesco’s development fraught with uncertainties and setbacks 105
Clinical trial data 107
Asmanex too late to have a big impact 110
CHAPTER 7 NOVEL ANTI-INFLAMMATORIES ANALYSIS AND FORECASTS 112
Definition of current comparator therapy 116
Targeting the leukotriene cascade 117
5-LO - Zileuton CR no competition for Singulair 119
cPLA2-antagonists are promising target 123
Chemokine inhibitors are a mixed group 125
CCR antagonists 125
CXCR antagonists 126
VLA-4 antagonists - many development failures 128
PDEIV inhibitors only promising in COPD? 130
Daxas 130
Other PDEIV inhibitors 134
Inhaled immunostimulatory DNA (ISS) 136
Targeting oligonucleotides 138
Other novel anti-inflammatories 140
CHAPTER 8 BIOLOGICALS ANALYSIS AND FORECASTS 144
Anti-IgE - Xolair to remains unchallenged 146
Anti-TNF-α 148
Promising in severe asthma... 148
...disappointing in COPD 150
Anti-IL-13 150
Anti-IL-5 152
Anti-IL-2 153
Other monoclonal antibodies targeting cytokines 154
CHAPTER 9 BRONCHODILATORS ANALYSIS AND FORECASTS 155
Competition for Spiriva on the horizon 155
Definition of current comparator therapy 157
LAS 34273 161
NVA 237 162
233705 164
Long-acting beta2-agonists will be once-daily 165
Definition of current comparator therapy 166
GSK’s once-daily LABAs 159797 and 542444 168
Indacaterol (QAB-149) 169
Clinical trial data 169
CHF-4226 171
Brovana 172
LABA/LAMA combination products have blockbuster potential in COPD 175
The SABA CFC-HFA switch in the US 179
Xopenex HFA 181
APPENDIX A 184
Methodology 184
Datamonitor forecast methodology 184
Bibliography 185
Epidemiology 185
Disease background 186
Clinical trial data 204
Press Releases 208
APPENDIX B 211
About Datamonitor 211
About Datamonitor Healthcare 211
Datamonitor Healthcare’s therapy area capabilities 212
About the Infectious Disease and Respiratory analysis team 213
Disclaimer 214
List of Tables
Table 1: Asthma prevalence and diagnosed population by country and age, 2006 21
Table 2: COPD prevalence by country and severity among adults over 45 years old, 2006 30
Table 3: Outcome measures for COPD 51
Table 4: Overview of asthma/COPD drug development pipeline, 2006 52
Table 5: GSK’s marketed respiratory portfolio, 2005 58
Table 6: AstraZeneca’s marketed respiratory portfolio, 2005 60
Table 7: Boehringer-Ingelheim’s marketed respiratory portfolio, 2005 62
Table 8: Key marketed and late-stage products for ICS/LABA combinations, 2006 69
Table 9: ICS/LABA combinations sales in the six major markets ($m), 2005-2015 69
Table 10: GSK is performing one study with 159797 and two with 642444 80
Table 11: Studies presented at the ERS Conference in September 2006 regarding Symbicort SMART 89
Table 12: Key marketed and late-stage products for inhaled corticosteroids, 2006 103
Table 13: ICS sales in the six major markets ($m), 2005-2015, $millions 104
Table 14: Key marketed and late-stage products for novel anti-inflammatories, 2006 113
Table 15: Key marketed and late-stage products for compounds affecting the leukotriene cascade, 2006 117
Table 16: Key products for CXCR2 agonists, 2006 126
Table 17: Key marketed and late-stage products for PDEIV inhibitors, 2006 134
Table 18: Key marketed and late-stage products for biologicals, 2006 144
Table 19: Key marketed and late-stage products for anticholinergics, 2006 155
Table 20: Long-acting anticholinergics sales in the six major markets ($m), 2005-2015 156
Table 21: Key marketed and late-stage products for LABAs, 2006 165
Table 22: Long-acting beta2-agonists sales in the six major markets ($m), 2005-2015 165
Table 23: GSK pool of LABA candidates in Phase II trials, 2006 168
List of Figures
Figure 1: Basic etiology of asthma 15
Figure 2: Classification of asthma by clinical, pretreatment features 16
Figure 3: Prevalence of asthma according to classification of severity 20
Figure 4: Key unmet needs in asthma, 2006 22
Figure 5: The allergic march is influences by several factors 24
Figure 6: Rate of decline of FEV1 with age in COPD patients 26
Figure 7: The inflammation associated with COPD involves neutrophils and alveolar macrophages 27
Figure 8: Classification of COPD as measured by airflow limitation 28
Figure 9: Prevalence of COPD at diagnosis according to classification of severity 29
Figure 10: Key unmet needs in COPD 31
Figure 11: Overview of asthma and COPD treatments, 2006 35
Figure 12: Appropriate LCM strategy depends on time and financial investment 46
Figure 13: Overview of forecasted asthma/COPD drugs in the pipeline, 2006 55
Figure 14: Key players in the asthma/CODP market, 2005 56
Figure 15: Pulmicort: a combination of strategies 65
Figure 16: GSK and AZ continue to develop their ICS/LABA combination products 66
Figure 17: Sepracor takes advantage of CFC-HFA switch in the US in 2008 67
Figure 18: ICS/LABA combinations sales in the six major markets ($m), 2005-2015 70
Figure 19: Warning in Advair prescribing information regarding salmeterol 71
Figure 20: Advair/Seretide and Symbicort sales in the six major markets, 2001-05 75
Figure 21: Formoterol is preferred LABA due to short onset of action, long duration and limited side effects 77
Figure 22: Characteristics of ICS/LABA drugs on the market and in development 78
Figure 23: ICS/LABA combination sales in the six major markets, 2005-15 82
Figure 24: Symbicort adjustable maintenance dosing 83
Figure 25: SMILE study design 86
Figure 26: ICS/LABA combinations sales in the six major markets, 2005-2015 90
Figure 27: Study design of two studies 93
Figure 28: Foster versus Advair/Seretide and Foster versus Symbicort, PEF 94
Figure 29: ICS/LABA combinations sales in the five major European markets, 2005-2015 96
Figure 30: ICS/LABA combinations sales in the six major markets, 2005-2015 98
Figure 31: Mometasone/indacaterol combination shows most promise for Novartis and Schering-Plough 99
Figure 32: ICS/LABA combinations sales in the six major markets, 2005-2015 100
Figure 33: ICS/LABA combinations sales in the six major markets, 2005-2015 102
Figure 34: ICS sales in the six major markets, 2005-2015 104
Figure 35: Study design and primary endpoint of ciclesonide 160µg versus 640µg 108
Figure 36: ICS sales in the six major markets, 2005-2015 110
Figure 37: ICS sales in the six major markets ($m), 2005-2015 111
Figure 38: Novel anti-inflammatory market is moving towards targeted therapy 114
Figure 39: Blockbuster potential of anti-inflammatories in COPD is uncertain, 2006-2020 115
Figure 40: Effect of tipelukast on inflammation cascade 118
Figure 41: Zileuton affects inflammatory cascade earlier than montelukast 120
Figure 42: Patient potential breakdown for Zileuton CR in the US 122
Figure 43: Singulair and Zileuton CR sales in the US ($m), 2005-2015 123
Figure 44: Efipladib affects inflammatory cascade earlier than montelukast and zileuton 124
Figure 45: Results from roflumilast RECORD and RATIO studies 132
Figure 46: Xolair sales in the six major markets, 2005-2015 148
Figure 47: Long-acting anticholinergics sales in the six major markets, 2005-2015 156
Figure 48: Respimat SMI demonstrates better lung deposition compared with conventional MDIs 159
Figure 49: The battle to be second to the once-daily LAMA market is between Almirall, Novartis and GSK 160
Figure 50: Long-acting anticholinergics sales in the six major markets, 2005-2015 161
Figure 51: Long-acting beta2-agonists sales in the six major markets ($m), 2005-2015 166
Figure 52: Long-acting beta2-agonists sales in the six major markets ($m), 2005-2015 167
Figure 53: Mean serum potassium over time 170
Figure 54: Patient potential breakdown for arformoterol in the US, 2006 173
Figure 55: Brovana sales in the US, 2005-2015 174
Figure 56: LABA/LAMA peak sales in the six major markets 175
Figure 57: Three possible LABA/LAMA combination drugs in development 177
Figure 58: The (levo)salbutamol market according to type of delivery device, 2005 180
Figure 59: The volume and sales values of the (levo)salbutamol market according to type of delivery device, 2005 181
Figure 60: Xopenex sales in the US, 2005-2015 182