Table of Contents

ABOUT DATAMONITOR HEALTHCARE 2
About the CNS pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Contributing experts 3
Datamonitor insight into the opioid market 4
Related reports 6
CHAPTER 2 MARKET OVERVIEW AND POTENTIAL 8
Market overview and pain definition 9
Definition of opioid market 9
Market potential 10
Epidemiology of pain 10
Incidence 10
The burden of pain on every day life 10
Commonly-reported pain conditions 10
Definition of pain 11
Nociceptive pain 11
Neuropathic pain 12
Types of pain treated with opioids 13
Diagnosis of pain 14
Treatment of pain 15
Acute pain and cancer pain 15
Chronic non-cancer pain 16
Unmet need in pain treatment 17
Need to reduce the abuse and overdosing potential of opioids 18
Need to minimize opioid-related adverse events 19
Improved short-acting opioids 20
Current market value and future market forecasts 26
Current market dynamics 26
OxyContin dominates the opioid market 26
The US generated more revenue from opioid therapies than the EU and Japan combined 27
The opioid market is set to grow throughout the forecast period 29
Short-acting opioids-large growth driver 30
Anti-abuse reformulations take share from OxyContin 32
Generics are ever present 33
CHAPTER 3 BRAND DYNAMICS AND LEADING COMPARATOR THERAPIES 34
Marketed brands overview 35
Short-acting opioid brands 36
Actiq (fentanyl oral transmucosal) 36
Drug overview 36
Forecasts to 2017 36
SWOT analysis 38
Clinical trial data 38
Fentora 40
Drug overview 40
Forecasts to 2017 40
SWOT analysis 44
Patient potential 44
Marketing factors 44
Clinical trial data 45
Long-acting opioid brand 47
OxyContin (oxycodone HCl controlled-release) 47
Drug overview 47
Forecasts to 2017 48
SWOT analysis 51
Clinical trial data 51
Kadian (morphine sulfate XR) 55
Drug overview 55
Forecasts to 2017 55
SWOT analysis 57
Clinical trial data 57
Avinza (morphine sulfate XR) 59
Drug overview 59
Forecasts to 2017 59
SWOT analysis 61
Clinical trial data 61
Duragesic (fentanyl transdermal patch) 63
Drug overview 63
Forecasts to 2017 64
SWOT analysis 66
Clinical trial data 66
Opana 68
Drug overview 68
Forecasts to 2017 69
SWOT analysis 70
Clinical trial data 70
CHAPTER 4 FORECAST ANALYSIS 72
Key events 73
New product launches 74
Key drug launch assumptions 74
Product launches in Japan 75
Patent expiries 76
Data definitions, limitations and assumptions 76
Standard units 76
Japanese market data 76
Derivation of sales forecasts and pricing trends 77
Forecast methodology 77
CHAPTER 5 STRATEGIES FOR SUCCESS 78
Broaden customer base with key additional indications 79
Back pain 80
Postoperative pain 80
Neuropathic pain 81
Osteoarthritis 81
Refractory migraine 82
Opportunities for specialized niche companies to enter the market 82
Delivery reformulation 83
Anti-abuse technologies 86
CHAPTER 6 PIPELINE OVERVIEW-R&D DYNAMICS AND APPROACH 87
Pipeline overview 88
Classification of pipeline products 91
Majority of pipeline products are reformulations of existing opioids 91
Short-acting opioids 91
Oral transmucosal opioids 91
Intranasal opioids 92
Oral inhaled opioids 92
Long-acting opioids 93
Oral opioids 93
Subcutaneous opioids 93
Transdermal opioids 93
Clinical trial design 94
Actiq clinical trials set the standard 94
Actiq pivotal trial overview 94
Clinical trial endpoints in pain 100
Primary endpoints: the brief pain inventory is often used to assess pain in cancer patients 100
Secondary endpoints: economic and quality-of-life measures are important 100
CHAPTER 7 SHORT-ACTING OPIOID DRUG ANALYSIS & FORECASTS 102
Late-stage short-acting pipeline overview 103
Fentanyl based formulations 105
Rapinyl (sublingual) 106
Drug overview 106
Forecasts to 2017 106
Marketing potential 109
Patient potential 111
Satisfaction of unmet needs 111
Clinical trial data 112
BEMA fentanyl (buccal) 112
Drug overview 112
Forecasts to 2017 113
Marketing factors 116
Patient potential 117
Satisfaction of unmet needs 118
Clinical trial data 118
Instanyl (intranasal) 119
Drug overview 119
Forecasts to 2017 119
Marketing potential 121
Patient potential 122
Satisfaction of unmet needs 122
Clinical trial data 123
Nasalfent (intranasal) 123
Drug overview 123
Forecasts to 2017 123
Marketing potential 125
Patient potential 126
Satisfaction of unmet needs 126
Clinical data 126
AD-923 (sublingual spray) 127
Drug overview 127
Ongoing clinical trial program 128
Forecasts to 2017 128
HFT-290 (transdermal) 130
Morphine-based formulations 131
Rylomine (intranasal) 131
Drug overview 131
Forecasts to 2017 131
Marketing potential 133
Patient potential 134
Satisfaction of unmet needs 134
Clinical trial data 134
Buprenorphine based formulations 135
V1003 (intranasal) 135
Drug overview 135
Forecasts to 2017 136
Marketing potential 138
Patient potential 138
Clinical trial data 139
BEMA LA (buccal) 140
Drug overview 140
Clinical trial data 140
Drugs on hold 141
Taifun (inhaled) 141
Drug overview 141
Marketing potential 141
Patient potential 142
Satisfaction of unmet needs 143
Clinical trial data 143
AeroLEF (inhaled) 144
Drug overview 144
Marketing potential 145
Patient potential 146
Satisfaction of unmet needs 146
Clinical trial data 147
CHAPTER 8 LONG-ACTING OPIOID DRUG ANALYSIS & FORECASTS 149
Late-stage long-acting pipeline overview 150
Oxycodone based formulations 153
Remoxy (oxycodone) 153
Drug overview 153
Forecasts to 2017 154
Marketing potential 156
Patient potential 157
Satisfaction of unmet needs 157
Clinical trial data 157
Oxytrex (oxycodone and naltrexone) 158
Drug overview 158
Forecasts to 2017 158
Marketing potential 161
Patient potential 161
Satisfaction of unmet needs 162
Ongoing clinical trial program 162
ELI-216 (naltrexone hydrochloride, oxycodone) 162
Drug overview 162
Marketing potential 163
Patient potential 163
Ongoing clinical trial program 163
Acurox/OxyADF (oxycodone) tablet 164
Drug overview 164
Clinical trial data 165
Morphine-based formulations 167
Embeda (morphine sulfate, naltrexone hydrochloride) 167
Drug overview 167
Forecasts to 2017 167
Marketing potential 170
Patient potential 170
Satisfaction of unmet needs 171
Clinical trial data 171
Morphine-6-glucuronide (M6G) 171
Drug overview 171
Forecasts to 2017 172
Marketing potential 173
Patient potential 174
Clinical trial data 174
Egalet morphine (morphine) 176
EpiCept MP/DP (morphine, lidocaine) 177
Drug overview 177
Tramadol-based formulations 177
Tapentadol 177
Drug overview 177
Forecasts to 2017 178
Marketing potential 180
Patient potential 180
Clinical trial data 181
Tramadol ER 182
Drug overview 182
Forecasts to 2017 182
Clinical trial data 182
NS-315 (tramadol hydrochloride) 183
Drug overview 183
BVF-146 (tramadol in combination with NSAID) 183
Other 184
Ionsys (transdermal delivery system) 184
Drug overview 184
Forecasts to 2017 184
Marketing potential 185
Patient potential 185
Clinical trial data 186
Sufentanil patch 188
Drug overview 188
Forecasts to 2017 188
Clinical trial data 189
Vicodin CR 190
Drug overview 190
Forecasts to 2017 190
Hydromorphone nasal spray 192
Drug overview 192
Clinical trial data 193
Q8003IR (morphine and oxycodone) 193
Drug overview 193
Clinical trial data 194
ADL-5859 194
Drug overview 194
Clinical trial data 195
Nalbuphine ER 195
Drug overview 195
Clinical trial data 196
NRP-290 196
Drug overview 196
Clinical trial data 196
MGX-001 197
Drug overview 197
Suspended drugs 197
Titragesia (fentanyl) 197
CHAPTER 9 EARLY-STAGE PROJECTS 198
Key Phase I and earlier opioids in development 199
Phase I overview 199
TPM-01/ Morphine 200
CR665 200
Clinical trial data 200
BIBLIOGRAPHY 202
Journal papers 202
Websites 207
DM reports 215
APPENDIX 216
Report methodology 216
Contributing experts 218
About Datamonitor 218
About Datamonitor Healthcare 218
About the CNS team 219
Disclaimer 220
List of Tables
Table 1: Primary opioid-related adverse events for 130 patients initially enrolled in the trial of Actiq for cancer-related breakthrough pain 19
Table 2: Characteristics of immediate-release opioids useful for breakthrough pain 21
Table 3: Side effects experienced in OxyContin clinical trials 53
Table 4: Forecast launch dates in the US and 5EU 74
Table 5: Forecast launch dates in Japan 75
Table 6: Pivotal patent expiries for key marketed drugs in the US and 5EU 76
Table 7: Key pipeline opioids in late-stage development , 2008 89
Table 8: Characteristics of patients enrolled in the Farrar Actiq trial 96
Table 9: Key short-acting opioids in late-stage development, 2008 105
Table 10: Key long-acting opioids in late stage development, 2008 152
Table 11: Opioids in Phase development, 2008 199
Table 12: Datamonitor drug assessment parameters 217
List of Figures
Figure 1: Historical (2006) and forecast (2007-17) sales revenue for key marketed and pipeline opioids across the 7MM 6
Figure 2: Key unmet needs in the opioid market 17
Figure 3: The current versus ideal approach to breakthrough pain treatment 22
Figure 4: Onset of action versus duration of action of opioid formulations 23
Figure 5: Opioid sales revenue trend, 7MM, 2004-E2007 26
Figure 6: Estimated sales revenue generated by opioids per molecule, 2007 27
Figure 7: Opioid sales by revenue, by region and country, 2006-17 28
Figure 8: Opioid total market value in the US, Japan and 5EU split by molecule, 2006-17 29
Figure 9: Opioid total market value in the US, Japan and 5EU, 2006-17 30
Figure 10: Short-acting opioids sales revenue ($m), 7MM, 2006-17 31
Figure 11: Sales revenue ($m) of key long-acting opioids, 2006-17 32
Figure 12: Historical sales revenue (2006-07) and forecast sales revenue (2008-17) for key opioids across the 7MM 35
Figure 13: Actiq sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 37
Figure 14: Actiq SWOT analysis 38
Figure 15: Fentora sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 42
Figure 16: Drug assessment summary for Fentora, 2008 43
Figure 17: Fentora SWOT analysis 44
Figure 18: OxyContin sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 49
Figure 19: Drug assessment summary for OxyContin, 2008 50
Figure 20: OxyContin SWOT analysis 51
Figure 21: Kadian sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 56
Figure 22: Kadian SWOT analysis 57
Figure 23: Avinza sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 60
Figure 24: Avinza SWOT analysis 61
Figure 25: Duragesic sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 65
Figure 26: Duragesic SWOT analysis 66
Figure 27: Opana franchise sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 69
Figure 28: Opana ER SWOT analysis 70
Figure 29: Impact of each key event on the opioid market across the seven major markets, 2007-12 73
Figure 30: Cephalon's breakthrough pain franchise, 2004-07 84
Figure 31: Cephalon's franchise as a percentage of Q1 2004 Standard Units 85
Figure 32: Drugs in development by class, 2008+ 88
Figure 33: Actiq study design 99
Figure 34: Historical (2006), estimated (2007) and forecast (2008-17) sales revenue for key short-acting pipeline opioids across the 7MM 103
Figure 35: Drug assessment summary overview of key pipeline short-acting opioids, 2008 104
Figure 36: Sales forecast for Rapinyl to 2017 in the 7MM 108
Figure 37: Drug assessment summary for Rapinyl, 2008 109
Figure 38: Sales forecast for BEMA Fentanyl to 2017 in the 7MM 115
Figure 39: Drug assessment summary for BEMA Fentanyl, 2008 116
Figure 40: Sales forecast for Instanyl to 2017 in the 7MM 120
Figure 41: Drug assessment summary for Instanyl, 2008 121
Figure 42: Sales forecast for Nasalfent to 2017 in the 7MM 124
Figure 43: Drug assessment summary for Nasalfent, 2008 125
Figure 44: Sales forecast for sublingual spray to 2017 in the 7MM 129
Figure 45: Drug assessment summary for sublingual spray, 2008 130
Figure 46: Sales forecast for Rylomine to 2017 in the 7MM 132
Figure 47: Drug assessment summary for Rylomine, 2008 133
Figure 48: Sales forecast for V1003 to 2017 in the 7MM 137
Figure 49: Drug assessment summary for V1003, 2008 138
Figure 50: Key long-acting opioid late-stage pipeline overview, 2008 150
Figure 51: Drug assessment summary overview of key pipeline long-acting opioids, 2008 151
Figure 52: Sales forecast for Remoxy to 2017 in the 7MM 155
Figure 53: Drug assessment summary for Remoxy, 2008 156
Figure 54: Sales forecast for Oxytrex to 2017 in the 7MM 160
Figure 55: Drug assessment summary for Oxytrex, 2008 161
Figure 56: Sales forecast for Embeda to 2017 in the 7MM 169
Figure 57: Drug assessment summary for Embeda, 2008 170
Figure 58: Sales forecast M6G to 2017 in the 7MM 172
Figure 59: Drug assessment summary for M6G, 2008 173
Figure 60: Sales forecast for Tapentadol to 2017 in the 7MM 179
Figure 61: Drug assessment summary for Tapentadol, 2008 180
Figure 62: Sales forecast for Ionsys to 2017 in the 7MM 185
Figure 63: Sales forecast for the Sufentanil patch to 2017 in the 7MM 189
Figure 64: Sales forecast for Vicodin CR to 2017 in the 7MM 191
Figure 65: Drug assessment summary for Vicodin CR, 2008 192