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

ABOUT DATAMONITOR HEALTHCARE 2 About the CNS pharmaceutical analysis team 2 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