Breakthrough Pain Fast-acting players will capture majority market share

ABOUT DATAMONITOR HEALTHCARE 2
About the Central Nervous System pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the breakthrough pain market 4
Summary 5
CHAPTER 2 PATIENT POTENTIAL 15
Definition of breakthrough pain 15
Epidemiology of breakthrough pain 16
Breakthrough cancer pain 16
Breakthrough pain is more prevalent in advanced cancer stages 16
Patients have between four to seven episodes per day 17
Breakthrough pain is a common cause of hospital admissions 18
Breakthrough pain in non-malignant diseases 18
Breakthrough pain also occurs in neuropathic, musculoskeletal, visceral and postoperative pain syndromes 18
Market sizing assumptions and caveats 19
Unmet need in breakthrough pain 21
Need for an analgesic that acts rapidly, predictably, and just for the duration of a breakthrough pain episode 22
Need for quick, simple, and safe drug administration 26
Need for improved convenience, cost, and safety of patient-controlled analgesia 27
Need to reduce the abuse and overdosing potential of opioids 28
Need to minimize opioid-related adverse events 29
Need for standardized diagnosis and assessment tools for breakthrough pain 30
CHAPTER 3 R&D APPROACH 33
Classification of pipeline products 33
Majority of pipeline products are reformulations of existing opioids 33
Oral transmucosal opioids 33
Oral inhaled opioids 34
Intranasal opioids 34
Subcutaneous opioids 34
Transdermal opioids 35
Clinical trial design in breakthrough pain 35
Actiq clinical trials set the standard 35
Actiq pivotal trial overview 36
Clinical trial endpoints in breakthrough pain 41
Primary endpoints: the Brief Pain Inventory is often used to assess pain in cancer patients 41
Secondary endpoints: economic and quality-of-life measures are important 41
CHAPTER 4 BREAKTHROUGH PAIN PIPELINE ANALYSIS 43
Pipeline overview 43
The success of Actiq and established efficacy make fentanyl a popular target 43
Key companies involved in the breakthrough pain pipeline 47
Cephalon: leading the way in breakthrough pain 47
Strong CNS focus is good for market growth 47
Follow-on drug strategy can offset generic incursion 48
Drug delivery expertise provides positive long term outlook 49
Leverage oncology resource to reach out to key treatment decision makers 49
Strategies for success 50
Broaden customer base with key additional indications 51
Back pain 52
Postoperative pain 53
Neuropathic pain 53
Osteoarthritis 53
Refractory migraine 54
CHAPTER 5 LATE-STAGE DRUG ANALYSIS & FORECASTS 56
Overview 56
Late stage pipeline summary 56
Definition of current comparator therapy 57
Comparison of key compounds 60
Comparative forecasts 60
Fentora 61
Profile 61
Drug overview 61
Clinical trial data 62
Patient potential 67
Marketing factors 69
Satisfaction of unmet needs 70
Forecasts to 2016 71
Datamonitor drug assessment summary 72
Rapinyl 73
Profile 73
Drug overview 73
Clinical trial data 74
Patient potential 74
Marketing factors 75
Satisfaction of unmet needs 77
Forecasts to 2016 77
Datamonitor drug assessment summary 79
BEMA Fentanyl 79
Profile 79
Drug overview 79
Clinical trial data 80
Patient potential 81
Marketing factors 82
Satisfaction of unmet needs 82
Forecasts to 2016 83
Datamonitor drug assessment summary 84
Intranasal morphine gluconate, Nastech 85
Profile 85
Drug overview 85
Clinical trial data 86
Patient potential 88
Marketing factors 88
Satisfaction of unmet needs 89
Forecasts to 2016 89
Datamonitor drug assessment summary 91
Rylomine (intranasal morphine) 91
Profile 91
Drug overview 91
Clinical trial data 92
Patient potential 93
Marketing factors 94
Satisfaction of unmet needs 95
Forecasts to 2016 95
Datamonitor drug assessment summary 96
PMI-150 (intranasal ketamine) 97
Profile 97
Drug overview 97
Clinical trial data 98
Patient potential 101
Marketing factors 101
Satisfaction of unmet needs 102
Forecasts to 2016 102
Datamonitor drug assessment summary 103
Fentanyl Taifun (oral inhaled fentanyl) 104
Profile 104
Drug overview 104
Clinical trial data 105
Patient potential 106
Marketing factors 107
Satisfaction of unmet needs 108
Forecasts to 2016 108
Datamonitor drug assessment summary 110
AeroLEF (oral inhaled fentanyl) 110
Profile 110
Drug overview 110
Clinical trial data 111
Patient potential 113
Marketing factors 114
Satisfaction of unmet needs 114
Forecasts to 2016 115
Datamonitor drug assessment summary 116
Other drugs 117
Titragesia (transdermal fentanyl patch) 117
Pain pen (subcutaneous hydromorphone injection) 118
TPM-01 (transdermal morphine cream) 119
AD-923 (sublingual fentanyl) 119
Nasalfent (intranasal fentanyl) 120
BIBLIOGRAPHY 121
Journal articles and conference abstracts 121
Websites 129
APPENDIX A 131
Contributing experts 131
Sales forecasts 132
Competitive positioning analysis of pipeline breakthrough pain drugs 133
Methodology 134
Datamonitor forecast methodology and assumptions 134
Product forecasts 134
Estimation of launch dates 134
Patient expiry and generic assumptions 134
Definition of a standard unit 136
APPENDIX B 137
About Datamonitor 137
About Datamonitor Healthcare 137
Datamonitor Healthcare's therapy area capabilities 138
About the CNS analysis team 139
Disclaimer 140
List of Tables
Table 1: Prevalence of breakthrough pain across the seven major markets, 2006 16
Table 2: Estimation of the breakthrough pain market across the seven major markets, 2005 19
Table 3: Characteristics of immediate-release opioids useful for breakthrough pain 23
Table 4: Primary opioid-related adverse events for 130 patients initially enrolled in the trial of Actiq for cancer-related breakthrough pain 30
Table 5: Characteristics of patients enrolled in the Farrar et al. (1998) Actiq trial 37
Table 6: Number of R&D projects in each class split by mode of delivery, 2006 43
Table 7: Clinical R&D pipeline for breakthrough pain drugs, 2006 44
Table 8: Cephalon's inline and pipeline pain product range, 2006 48
Table 9: Key products in late-stage R&D pipeline for breakthrough pain, 2006 56
Table 10: Primary opioid-related adverse events for 130 patients initially enrolled in the trial of Actiq for cancer-related breakthrough pain 58
Table 11: Pharmacokinetic parameters in adult subjects receiving the various doses of Actiq 59
Table 12: Fentora product claims on www.fentora.com 62
Table 13: Key approval and launch dates impacting Fentora's revenue forecast, 2006-2016 71
Table 14: Key approval and launch dates impacting Rapinyl's revenue forecast, 2006-2016 78
Table 15: BEMA technology product claims taken from BioDelivery Sciences's website 80
Table 16: Key approval and launch dates impacting BEMA Fentanyl revenue forecast, 2006-2016 83
Table 17: Key approval and launch dates impacting intranasal morphine gluconate revenue forecast, 2006-2016 90
Table 18: Key approval and launch dates impacting Rylomine revenue forecast, 2006-2016 95
Table 19: Key approval and launch dates impacting PMI-150 revenue forecast, 2006-2016 102
Table 20: Key approval and launch dates impacting Fentanyl Taifun revenue forecast, 2006-2016 109
Table 21: Key approval and launch dates impacting AeroLEF revenue forecast, 2006-2016 115
Table 22: Datamonitor's forecast sales of pipeline breakthrough pain drugs and the total breakthrough pain market across the seven major markets ($m), 2006-2016 132
Table 23: Summary of commercial and research/clinical attractiveness of late-stage drugs for breakthrough pain 133
Table 24: Estimation of launch dates by phase of development 134
Table 25: Estimated generic discounts by country, 2006* 135
Table 26: Estimates of brand erosion by following patent expiry by country 135
List of Figures
Figure 1: Datamonitor's breakthrough pain forecast market across the seven major markets, 2006-2016 5
Figure 2: Datamonitor breakthrough pain drug assessment summary, 2006-2016 6
Figure 3: The different types of breakthrough pain 17
Figure 4: The current versus ideal approach to breakthrough pain treatment 24
Figure 5: Onset of action versus duration of action of opioid formulations 25
Figure 6: Actiq study design 40
Figure 7: Breakthrough pain drug pipeline by development phase and formulation, 2006 46
Figure 8: Breakdown of the breakthrough pain pipeline by formulation, 2006 46
Figure 9: Breakdown of the pipeline by molecule, 2006 47
Figure 10: Difference in pain intensity between Actiq and placebo (ITT analysis) 57
Figure 11: Pain relief of Actiq versus placebo (ITT analysis) 58
Figure 12: Datamonitor's comparative forecast of sales for key products across the seven major markets ($m), 2006-2016 60
Figure 13: Pain intensity difference of Fentora versus placebo over time 63
Figure 14: Comparison of pain intensity difference scores of Actiq versus Fentora 65
Figure 15: Datamonitor's forecast of sales for Fentora across the seven major markets ($m), 2006-2016 72
Figure 16: Datamonitor's competitive positioning analysis for Fentora, 2006-2016 73
Figure 17: Datamonitor's forecast of sales for Rapinyl across the seven major markets ($m), 2006-2016 78
Figure 18: Datamonitor's competitive positioning analysis for Rapinyl, 2006-2016 79
Figure 19: Datamonitor's forecast of sales for BEMA Fentanyl across the seven major markets ($m), 2006-2016 84
Figure 20: Datamonitor's competitive positioning analysis for BEMA Fentanyl, 2006-2016 85
Figure 21: Datamonitor's forecast of sales for Intranasal morphine gluconate across the seven major markets ($m), 2006-2016 90
Figure 22: Datamonitor's competitive positioning analysis for Intranasal morphine gluconate, 2006-2016 91
Figure 23: Datamonitor's forecast of sales for Rylomine across the seven major markets ($m), 2006-2016 96
Figure 24: Datamonitor's competitive positioning analysis for Rylomine, 2006-2016 97
Figure 25: PMI-150 study design 99
Figure 26: Datamonitor's forecast of sales for PMI-150 across the seven major markets ($m), 2006-2016 103
Figure 27: Datamonitor's competitive positioning analysis for PMI-150, 2006-2016 104
Figure 28: Datamonitor's forecast of sales for Fentanyl Taifun across the seven major markets ($m), 2006-2016 109
Figure 29: Datamonitor's competitive positioning analysis for Fentanyl Taifun, 2006-2016 110
Figure 30: Datamonitor's forecast of sales for AeroLEF across the seven major markets ($m), 2006-2016 116
Figure 31: Datamonitor's competitive positioning analysis for AeroLEF, 2006-2016 117