Table of Contents
Drug Delivery Innovation in Inhalation Executive summary 10
Introduction 10
Respiratory diseases 11
Non-respiratory indications 12
New opportunities 12
Case studies 13
Specialist companies 14
New developments & market opportunities 15
Chapter 1 Introduction 18
Summary 18
Advantages of lung delivery of drugs 19
Formulations and devices 19
Nebulizers 19
Metered dose inhalers 20
Dry powder inhalers 21
Inhaled drug market 21
Respiratory diseases 22
Respiratory infections 24
Systemic diseases 25
An entry barrier for generics 25
Devices and innovation 26
New therapeutic opportunities 27
Chapter 2 Respiratory indications 30
Summary 30
Introduction 31
Respiratory diseases 31
Overview 31
Asthma 31
COPD 32
Cystic fibrosis 33
Rationale for using inhaled therapeutics 34
Devices 35
Innovation 35
Types of device 36
Nebulizers 38
Metered dose inhalers 39
Dry powder inhalers 40
Soft mist inhalers 41
Current classes of inhaled drug 42
Short acting 2 agonists 42
Long acting 2 agonists 44
Muscarinic antagonists 45
Corticosteroids 46
Combination products 48
2 agonists and anticholinergics 49
Corticosteroids and LABA 49
Chapter 3 Non-respiratory indications 54
Summary 54
Introduction 55
Strategic rationale 55
Delivery requirements 56
Respiratory infections 56
Pulmonary hypertension 57
Diabetes 59
Chapter 4 New opportunities 62
Summary 62
Introduction 63
New indications 63
Diabetes 64
CNS diseases 65
Migraine 66
Pain 67
Sexual dysfunction 67
Cancer 68
Vaccines 68
Antibiotics 68
New respiratory targets 69
Dual 2 agonists and Muscarinic antagonists (MABA) 70
Avoiding side effects 72
Ion channel modulators 73
Protein therapeutics 73
Oligonucleotides 76
New respiratory products 77
Monotherapies 78
Combination products 82
Chapter 5 Case studies 88
Summary 88
Introduction 89
Pulmicort 89
Formulation 89
Commercial 90
Strategy 92
Flutiform 93
Strategy 95
Commercial 96
Approval 97
Exubera 98
The device 99
Other issues 100
The cost to Pfizer 101
Conclusion 103
Chapter 6 Specialist companies 106
Summary 106
Introduction 107
3M Drug Delivery Systems 107
Activaero Technologies 108
airPharma 108
Akela Pharma 108
Alexza Pharmaceuticals 109
Alkermes 110
Almirall Sofotec 110
Altair Therapeutics 111
Aradigm 111
Battelle 112
Cambridge Consultants 112
Dance Pharmaceuticals 113
Direct-Haler A/S 113
Enhanced Pharmaceuticals 113
Inhaleness BV 114
IVAX 114
Kamada 114
Mannkind 115
MAP Pharmaceuticals 116
Meda AB 117
MicroDose Therapeutix 117
Nektar Therapeutics 119
Novaliq GmbH 119
Omron Healthcare 120
Oriel Therapeutics 120
Orion Corp. 121
PARI Pharma 121
Pearl Therapeutics 122
Prosonix 123
Respirics 123
Skye Pharma 124
Vectura Group 125
Chapter 7 New developments & market opportunities 128
Summary 128
New developments 129
Regulatory perspective 129
Inhaled particle distribution 130
Formulation technologies 131
Propellants 131
New aerosol generation approaches 133
Particle engineering 134
Inhaler technologies 136
DPIs 136
MDIs 138
Other inhalers 141
Biologic therapeutics 142
Oligonucleotides 142
Proteins 142
Deals and collaborative opportunities 144
Market opportunities 146
Drug types 146
New indications 146
Generic opportunities 147
Commercial deals 148
Appendix 149
Bibliography 149
Glossary 152
Index 154
List of Figures
Figure 1.1: Inhaled drug market share by indication 22
Figure 1.2: The dominance of the respiratory market by inhaled therapies 23
Figure 2.3: Opportunities for innovation 36
Figure 2.4: 2008 Market share breakdown of the respiratory market by inhaler device type 37
Figure 2.5: Product share of short acting 2 agonists, 2008 43
Figure 2.6: Devices used for short acting 2 agonists 44
Figure 2.7: US sales of Advair, Serevent and Flixotide ($m), 2000-08 51
Figure 5.8: Pulmicort sales ($m) & impact of new delivery forms, 1991-2009 91
Figure 5.9: Exubera inhalation device 100
Figure 5.10: Exubera – the cost of failure 102
Figure 7.11: Semi-fluorinated alkanes (SFAs) 132
Figure 7.12: Improving MDIs 139
List of Tables
Table 2.1: Time line of key developments in inhaler technology 37
Table 2.2: Significant branded inhaled steroid products 47
Table 2.3: Inhaled corticosteroid plus LABA combination formulations 50
Table 4.4: Inhaled formulations in development for CNS conditions 65
Table 4.5: Inhaled NCE formulations in development for respiratory diseases 71
Table 4.6: Long acting agonists in clinical development 80
Table 4.7: Long acting muscarinic antagonists in clinical development 82
Table 4.8: New Steroid + LABA combination formulations in development 85
Table 4.9: Muscarinic antagonist combination formulations in development 86
Table 6.10: Alexza's Staccato formulations in development 110
Table 6.11: Aradigm's development pipeline of inhaled formulations 112
Table 6.12: MAPP's development pipeline of inhaled formulations 117
Table 6.13: MicroDose's development pipeline of inhaled formulations 118
Table 6.14: Oriel's development pipeline of inhaled formulations 121
Table 6.15: PARI Pharma's development pipeline of inhaled formulations 122
Table 6.16: Vectura's development pipeline of inhaled formulations 126
Table 7.17: Summary of characteristics of newer DPIs 137