Forecast Insight: Opioids - Saturation limits the commercial potential of individual brands

CHAPTER 1 EXECUTIVE SUMMARY 3
Strategic scoping and focus 3
Datamonitor insight into the disease market 3
Related reports 6

CHAPTER 2 MARKET DEFINITION AND OVERVIEW 8
Market definition for this report 8
Countries and regions included in this report 8
Seven major market assessment 10
Market segmentation 10
Total market forecasts 11
Rest of the world snapshot 13
Global market value 13
Global market volume 14
Rest of the world breakdown 17

CHAPTER 3 BRAND DYNAMICS - LONG-ACTING OPIOIDS 18
Overview of competitive landscape 18
Seven major market forecasts - long-acting opioids 18
Key brands across the seven major pharmaceutical markets 21
Update on the key marketed brands 23
OxyContin (oxycodone controlled-release, Purdue, Mundipharma, Napp) 23
Background and current market position - market leading brand 23
Recent events - strong sales following re-establishment of market exclusivity 23
Datamonitor comments and forecasts - anti-abuse versions set to shrink market share 23
Duragesic (fentanyl patch, Johnson & Johnson) 26
Background and current market position - available across all seven major markets 26
Recent events- additional generic manufacturers enter the market 27
Datamonitor comments and forecasts - branded value holds in the five major European markets 27
Kadian (morphine extended-release, Actavis) 28
Background and current market position - leading morphine brand 28
Recent events - King sells rights to Actavis following Alpharma acquisition 28
Datamonitor comments and forecasts - King concentration on Avinza 29
Avinza (morphine extended-release, King Pharmaceuticals) 30
Background and current market position - marginal historical growth 30
Recent events - King retains Avinza after its acquisition of Alpharma 31
Datamonitor comments and forecasts - switching to Embeda is likely 31
Opana extended-release (oxymorphone extended-release, Endo) 32
Background and current market position - first oral availability of molecule 32
Recent events - new doses launched 33
Datamonitor comments and forecasts - no clear differentiation from current opioids 33
Update on key pipeline drugs - anti-abuse technologies 35
Drivers to anti-abuse technologies 35
Enhanced media attention on opioid abuse in the US 35
Cost premium could limit uptake 37
Label changes unlikely 38
Patent challenges 39
Remoxy (oxycodone, Pain Therapeutics and King Pharmaceuticals) 39
Background - gelatin abuse-deterrent capsule 39
Recent events - delay due to additional data request 40
Datamonitor comments and forecasts - launch expected in late 2009 41
ELI-216 (oxycodone and naltrexone, Elite Pharmaceuticals) 42
Background - oxycodone and sequestered naltrexone 42
Recent events - Phase III trial planned 43
Datamonitor comments and forecasts - Elite likely to need a partner 44
Embeda (morphine and naltrexone, King Pharmaceuticals) 45
Background -the only morphine abuse-deterrent formulation in development 45
Recent events - product under FDA review 45
Datamonitor comments and forecasts 46
Oxytrex (oxycodone and naltrexone, Pain Therapeutics) 47
Background - targeting tolerance and dependence 47
Recent events - development progress not published 48
Datamonitor comments and forecasts - a high-risk, high-gain product 49
Update on other key pipeline drugs 50
Targin (oxycodone hydrochloride and naloxone, Mundipharma) 50
Background - targets gastrointestinal side effects 50
Recent events - Targin submitted for approval in the EU 51
Datamonitor comments and forecasts - an interesting lifecycle management strategy 51
Sufentanil patch (sufentanil, Durect) 53
Background - seven days of relief in one patch 53
Recent events - Endo pulls out of marketing 53
Datamonitor comments and forecasts - commercial potential affected by Endo withdrawal 54
Vicodin CR (hydrocodone bitartrate and acetaminophen controlled-release, Abbott) 55
Background - reformulation lifecycle management strategy 55
Recent events - Complete Response letter from the FDA 55
Datamonitor comments and forecasts - no clear benefit over parent drug 56
Tapentadol ER (tapentadol, Johnson & Johnson and Grünenthal) 57
Background - super tramadol 57
Recent events - positive clinical data publication 57
Datamonitor comments and forecasts - commercial success dependent on the results of full clinical trial program 60

CHAPTER 4 BRAND DYNAMICS - SHORT- AND RAPID-ACTING OPIOIDS 62
Overview of competitive landscape 62
Breakthrough pain 62
Seven major market forecasts - Short- and rapid-acting opioids 63
US market growth 65
Five major European market growth 68
Japan - no products yet available 71
Leading brands across the seven major pharmaceutical markets 73
Current market dynamics - sales data reveal market slowdown in the US 74
Pre-launch of Fentora and Actiq generics in the US (Q3 2003-Q3 2006) 75
Market falls after launch of Fentora and Actiq generics in the US 75
Factors contributing to decline in market volume 79
Market assumptions 80
Regulatory approvals and off-label prescribing pattern 80
Key differentiating factors for pipeline drugs 82
Speed of action 82
Marketing capabilities 83
Overdose and misuse potential 87
Differentiation from currently marketed brands 89
Key marketed brands 89
Actiq (transmucosal fentanyl, Cephalon) 89
Background - first product on the market 89
Recent events - strong growth in Europe 89
Datamonitor comments and forecasts - launch in Japan 90
Fentora (buccal fentanyl, Cephalon) 91
Background - follow-on product 91
Recent events - European launch 92
Datamonitor comments and forecasts - approval for non-cancer pain key 94
Ionsys (fentanyl iontophoretic transdermal system, Johnson & Johnson) 95
Background - failed delivery technology 95
Recent events - launched then withdrawal 95
Datamonitor comments - no way back 96
Update on key pipeline drugs - dissolvable formulations 96
Onsolis (buccal disc fentanyl, Meda and BioDelivery sciences) 96
Background - dissolvable polymer disc 96
Recent events - FDA approval and launch nears 97
Datamonitor comments and forecasts - strong EU marketing partner 97
Abstral (formerly Rapinyl, sublingual dissolvable tablet fentanyl, ProStrakan and Orexo) 98
Background - dissolvable fentanyl tablet for sublingual administration 98
Recent events - Endo withdraws from US marketing 98
Datamonitor comments and forecasts - US market potential limited 99
Update on key pipeline drugs - spray formulations 100
Instanyl (intranasal fentanyl, Nycomed) 100
Background - unlikely to be developed for the US market 100
Recent events - still in pre-registration in Europe 101
Datamonitor comments and forecasts - no US development 101
NasalFent (intranasal fentanyl, Archimedes) 102
Background - most rapid onset of action 102
Recent events - additional clinical trial data 102
Datamonitor comments and forecasts - no marketing partner 103
Rylomine (intranasal morphine, Javelin) 104
Background - morphine based 104
Recent events - no news 104
Datamonitor comments and forecasts - differentiated product 105
AD-923 (sublingual spray fentanyl, Sosei) 106
Background - commercial partner dropped, development partner sought 106
Datamonitor comments and forecasts - launch ex-Japan not forecast 107
Fentanyl TAIFUN (inhaled fentanyl, Johnson & Johnson, Akela, and Teikoku Seiyaku) 108
Background - Big Pharma marketing partner 108
Datamonitor comments and forecasts 109

CHAPTER 5 BRAND DYNAMICS - CONVENTIONAL OPIOIDS 111
Overview of competitive landscape 111
Update on key pipeline drugs 111
Acurox (oxycodone and niacin, Acura Pharmaceuticals, King Pharmaceuticals) 111
Background - King Pharmaceuticals' immediate-release anti-abuse product 111
Recent events - submission to the FDA 112
Datamonitor comments and forecasts - cost premium limits uptake 112
Morphine-6-glucuronide (Morphine metabolite, Paion) 114
Background - metabolite of morphine 114
Recent events - Paion acquires CeNeS 114
Tapentadol IR 115
Background - dual mechanism of action 115
Recent events - US approval in 2008 115
Datamonitor comments and forecasts - launch imminent 116

BIBLIOGRAPHY 118
Journal papers 118
Websites 118
Datamonitor reports 126

APPENDIX A - MARKET ASSUMPTIONS 127
New product launches 127
Patent expiries 128
Data definitions, limitations and assumptions 128
Standard units 128
Japanese market data 128
Derivation of sales forecasts and pricing trends 129
Forecast methodology 129

APPENDIX B 130
Contributing experts 130
Conferences attended 130
Report methodology 130
About Datamonitor 130
About Datamonitor Healthcare 131
About the CNS analysis team 132
Disclaimer 133

List of Tables
Table 1: Sales forecasts for the opioids market, sub-markets and key brands in the seven major markets ($m), 2007-2018 12
Table 2: Updated key long-acting opioid brands by 2007 sales revenue across the seven major markets ($m) 21
Table 3: Key long-acting opioids in the late-stage R&D pipeline, 2009 22
Table 4: Tapentadol Phase III clinical trial program, 2009 59
Table 5: Short- and rapid-acting opioid brands by 2007 sales revenue across the seven major markets ($m), 2007-2018 73
Table 6: Key short- and rapid-acting opioids in the late-stage R&D pipeline, 2009 74
Table 7: Companies planning to market short- and rapid-acting opioid drugs, 2009 84
Table 8: Datamonitor's estimated launch dates for opioid products in the seven major markets, 2009-2018 127
Table 9: Key patent expiry dates for the approved opioid brands in the seven major markets, 2009-2018 128

List of Figures
Figure 1: Overlap in opioid subclasses 10
Figure 2: Total opioids market value ($ billion), 2007-2018 11
Figure 3: Global opioid market sales by region ($m), 2007 13
Figure 4: Change in global opioid market sales revenue by region, 2004-07 14
Figure 5: Global opioid market split by volume (IMS Standard Units), 2007 15
Figure 6: Global opioid market sales by volume (IMS Standard Units), 2004-07 16
Figure 7: Rest of world opioid sales by region ($m), 2007 17
Figure 8: Long-acting opioids sales in the seven major markets, 2005-2018 20
Figure 9: Sales by volume (IMS Standard Units) for oxycodone controlled-release (branded and generics) in the US, 2005-08 24
Figure 10: OxyContin sales revenue estimates ($m) in the US, 2007-08 25
Figure 11: OxyContin (oxycodone extended-release) sales ($m) across the seven major markets, 2007-2018 26
Figure 12: Duragesic (and other fentanyl patch brands) sales ($m) across the seven major markets, 2007-2018 28
Figure 13: Kadian (morphine extended-release) sales ($m) across the seven major markets, 2007-2018 30
Figure 14: Avinza (morphine controlled-release) sales ($m) in the US, 2007-2018 32
Figure 15: Opana ER (oxymorphone extended-release) sales ($m) in the US, 2007-2018 34
Figure 16: Misuse of oral opioid formulations 35
Figure 17: Demand for each technology by key stakeholders 38
Figure 18: Remoxy's abuse and misuse potential 40
Figure 19: Remoxy (oxycodone controlled-release gel cap) sales ($m) across the US, 2009-2018 42
Figure 20: ELI-216's abuse and misuse potential 43
Figure 21: ELI-216 (oxycodone controlled-release and naltrexone) sales ($m) across the US, 2011-2018 44
Figure 22: Embeda's abuse and misuse potential 45
Figure 23: Embeda (morphine controlled-release) sales ($m) in the US, 2009-2018 47
Figure 24: Oxytrex abuse and misuse potential 48
Figure 25: Oxytrex sales ($m) across the US, 2010-2018 50
Figure 26: Targin (morphine controlled-release and naloxone) sales ($m) in the 5EU, 2007-2018 53
Figure 27: Sufentanil patch sales ($m) in the US and 5EU, 2011-2018 55
Figure 28: Vicodin CR (hydrocodone and acetaminophen controlled-release) sales ($m) in the US, 2010-2018 57
Figure 29: Tapentadol ER sales ($m) across the US and 5EU, 2010-2018 61
Figure 30: Short- and rapid-acting opioids market across the seven major markets, 2007-2018 64
Figure 31: Short- and rapid-acting branded opioid sales ($m) across the seven major markets, 2007-2019 65
Figure 32: Short- and rapid-acting opioids market ($m) in the US, 2007-2018 67
Figure 33: Short- and rapid-acting branded opioid sales ($m) in the US, 2007-2018 68
Figure 34: Short- and rapid-acting opioids market ($m) in the five major European markets (5EU), 2007-2018 69
Figure 35: Short- and rapid-acting branded opioid sales ($m) across the five major European markets, 2007-2018 70
Figure 36: Short- and rapid-acting opioids market ($m) in Japan, 2010-2018 71
Figure 37: Short- and rapid-acting opioid brands sales ($m) in Japan, 2010-2018 72
Figure 38: Quarterly change in IMS Standard Units sold for Actiq, generic Actiq and Fentora in the US, Q3 2003-Q2 2008 76
Figure 39: Quarterly change in sales revenue for Actiq, generic Actiq and Fentora in the US, Q3 2003-Q2 2008 77
Figure 40: Quarterly price per IMS Standard Unit for Actiq, generic Actiq and Fentora in the US, Q3 2003-Q2 2008 78
Figure 41: Quarterly change in combined IMS Standard Units sold for Actiq, generic Actiq and Fentora in the US, Q3 2003-Q2 2008 79
Figure 42: Quarterly sales for Fentora in the US, and Actiq in the 5EU ($m), and non-DTC promotional spend ($m), Q1 2007-Q2 2008 80
Figure 43: Key differentiating factors for pipeline agents in the short- and rapid-acting opioids market, 2009 82
Figure 44: Time to significant analgesia (minutes) 83
Figure 45: Quarterly change in sales revenue for Actiq in the five major European markets, Q3 2003-Q2 2008 90
Figure 46: Actiq (transmucosal fentanyl) sales ($m) across the seven major markets, 2007-2018 91
Figure 47: Fentora (buccal fentanyl) sales ($m) across in the US and 5EU, 2007-2018 94
Figure 48: Image of Ionsys fentanyl patch system 95
Figure 49: Onsolis (buccal fentanyl) sales ($m) in the US and 5EU, 2009-2018 98
Figure 50: Abstral (sublingual fentanyl) sales ($m) across the seven major markets, 2009-2018 100
Figure 51: Instanyl (intranasal fentanyl) sales ($m) in the five major European markets, 2009-2018 102
Figure 52: NasalFent (intranasal fentanyl) sales ($m) across the US and 5EU, 2010-2018 104
Figure 53: Rylomine (intranasal morphine) sales ($m) across the US and 5EU, 2010-2018 106
Figure 54: AD-923 (sublingual spray fentanyl) sales ($m) in Japan, 2012-2018 108
Figure 55: Fentanyl TAIFUN (inhaled fentanyl) sales ($m) across the seven major markets, 2011-2018 110
Figure 56: Acurox's abuse and misuse potential 112
Figure 57: Acurox (oxycodone and niacin) sales ($m) in the US, 2009-2018 113
Figure 58: Tapentadol IR sales ($m) in the US and 5EU, 2009-2018 117