Pipeline and Commercial Insight: Neuropathic Pain - UCB's Vimpat set to compete with major players

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 Neuropathic pain market 4

Key metrics 6

Datamonitor pipeline assessment summary 10

Related reports 10

CHAPTER 2 NEUROPATHIC PAIN - MARKET OVERVIEW AND POTENTIAL 12

Definition of neuropathic pain 13

Segmentation of neuropathic pain 14

Segmentation of neuropathic pain differs depending on the geographic market 14

General neuropathic pain provides a broader customer base in the EU 15

US approval requires evidence in each neuropathic pain subtype 15

Major neuropathic pain subtypes 16

Diabetic neuropathic pain 16

Post-herpetic neuralgia 16

HIV neuropathic pain 17

Neuropathic low-back pain 17

Other subtypes 18

Epidemiology 18

Diabetic neuropathic pain 20

Post-herpetic neuralgia 21

HIV neuropathic pain 22

Post-operative pain 22

Current market overview 23

Five treatments are currently marketed for neuropathic pain 23

Off-label prescribing 24

US dominated market 27

Unmet need in neuropathic pain 28

Clinical unmet need 28

1. Improved efficacy 29

2. Improved side-effect profile 30

3. Reduced time to onset of action 30

4. Fewer drug-drug interactions 31

5. Pill burden 31

Clinical trial design in neuropathic pain 32

Choice of endpoint is the key clinical trial design factor in neuropathic pain 32

Head-to-head trials of increasing importance 32

Lyrica is the ideal choice of comparator drug for head-to-head clinical trials 32

Length of trial should indicate titration period for physician ease of use 32

The Initiative on Methods, Measurements and Pain Assessments in Clinical trials (IMMPACT) 33

European Federation of Neurological Societies assessment 35

Clinical trial endpoints in neuropathic pain 35

50% reduction in pain is a primary measure of efficacy 35

Multiple pain and quality of life assessment questionnaires should be used in trials 35

Clinical trial drop-out as an endpoint 40

CHAPTER 3 BRAND DYNAMICS AND LEADING COMPARATOR THERAPIES 41

Marketed brands overview 42

Lyrica (pregabalin) 42

Drug overview 42

Forecasts to 2017 43

SWOT 44

Datamonitor drug assessment summary 45

Clinical trial data 45

Lyrica clinical trial 1 46

Lyrica clinical trial 2 46

Lyrica clinical trial 3 47

Neurontin (gabapentin) 48

Drug overview 48

Forecasts to 2017 49

SWOT 50

Clinical trial data 50

Lidoderm (lidocaine) 51

Drug overview 51

Forecasts to 2017 52

Clinical trial data 53

Lidoderm clinical trial 1 53

Lidoderm clinical trial 2 54

Cymbalta (duloxetine) 55

Drug overview 55

Forecasts to 2017 56

SWOT 57

Clinical trial data 57

Tegretol (carbamazepine) 58

Drug overview 58

SWOT 59

CHAPTER 4 FORECAST ANALYSIS 60

Key events 61

New product launches 62

Product launches in Japan 62

Patent expiries 63

Cymbalta 63

Lidoderm 63

Data definitions, limitations and assumptions 65

Standard units 65

Japanese market data 65

Derivation of sales forecasts and pricing trends 65

Forecast methodology 65

CHAPTER 5 STRATEGIES FOR SUCCESS 66

Key R&D company strategies 67

Reformulation strategies: Gabapentin 67

Gabapentin GR 67

XP13512 68

Patient subgroups 68

CHAPTER 6 PIPELINE OVERVIEW AND DYNAMICS 72

Pipeline overview 73

Classification of pipeline products 74

Glutamate receptor modulators 74

NMDA 74

AMPA 75

Kainate 75

Ion channel modulators 76

Sodium channels 76

Calcium channels 76

GABA modulators 76

Others 77

SNRIs 77

Dopamine modulators 78

Cannabinoid agonists 78

Vanilloid receptor agonists 78

Substance P release modulators 79

ACh receptor agonists 79

NGF modulators 79

TNF alpha antagonists 79

Adrenoceptor modulation 79

Adenosine A2 agonists 80

Free radicals 80

Phase II and above 80

Key companies involved in the neuropathic pain pipeline 84

Pfizer 84

Neurontin 85

Lyrica 86

Eli Lilly 89

Cymbalta 89

UCB 90

Vimpat 91

Brivaracetam 91

Discontinued and suspended projects 92

Projects recently suspended or discontinued 92

ACV-1 92

Pristiq 92

Radafaxine (353162) 94

Lamictal XR 95

Namenda (memantine) 97

Traxoprodil 97

AZD-4282 98

CHAPTER 7 LATE-STAGE DRUG ANALYSIS & FORECASTS 99

Glutamate receptor modulators 100

Pipeline summary 100

Comparative forecasts 102

Definition of current comparator therapy 102

Pfizer's Lyrica is Datamonitor's comparator therapy 102

Lidoderm is the topical comparator therapy 106

Zenvia (dextromethorphan & quinidine sulfate) 107

Drug overview 107

Forecasts to 2017 108

Datamonitor drug assessment summary 109

Patient potential 110

Marketing factors 111

Satisfaction of unmet needs 112

Clinical trial data 113

NP-1 (ketamine & amitriptyline) 114

Drug overview 114

Forecasts to 2017 114

Datamonitor drug assessment summary 116

Patient potential 117

Marketing factors 118

Satisfaction of unmet needs 119

Clinical trial data 119

Other glutamate receptor modulators 121

CNS-5161 121

V3381 124

RGH-896 128

EVT 101 128

NS-1209 129

NGX-426 129

Ion channel modulators 130

Pipeline summary 130

Comparative forecasts 132

Definition of current comparator therapy 132

Vimpat (lacosamide) 133

Drug overview 133

Forecasts to 2017 133

Datamonitor drug assessment summary 134

Patient potential 135

Marketing factors 136

Satisfaction of unmet needs 137

Clinical trial data 138

Ralfinamide 141

Drug overview 141

Forecasts to 2017 142

Datamonitor drug assessment summary 143

Patient potential 144

Marketing factors 145

Satisfaction of unmet needs 145

Clinical trial data 146

Other ion channel modulators 149

Retigabine 149

Bupivacaine (Eladur) 150

Lidocaine patch KN-48 151

Brivaracetam 151

GABA receptor modulators 152

Pipeline summary 152

Comparative forecasts 154

Definition of current comparator therapy 154

XP13512 154

Drug overview 154

Forecasts to 2017 155

Datamonitor drug assessment summary 157

Marketing factors - improved duration of action 158

Patient potential 159

Satisfaction of unmet needs 159

Clinical trial data 159

Gabapentin GR 161

Drug overview 161

Forecasts to 2017 161

Datamonitor drug assessment summary 162

Clinical trial data 163

Other therapies 167

Pipeline summary 167

Comparative forecasts 169

Transacin (NGX-4010) 170

Drug overview 170

Forecasts to 2017 170

Datamonitor drug assessment summary 172

Patient potential 173

Marketing factors 173

Satisfaction of unmet needs 174

Clinical trial data 175

Other drugs 178

Sativex (GW-1000) 178

Fentora (fentanyl buccal transmucosal) 184

BVT.115959 184

Bicifadine 186

NSD-644 187

Reboxetine (+)-(S,S) 187

F13640 187

AS-3201 188

KD7040 188

Ibudilast (AV411) 188

IP 751/CT-3 (ajulemic acid) 189

ADL5859 190

KDS-2000 190

AGN 203818 190

681323 190

Liposomal galantamine 191

TAK-583 191

Botulinum toxin type A-hemagglutinin complex (Dysport) 191

Zucapsaicin 191

2PX 191

CHAPTER 8 INNOVATIVE EARLY-STAGE PROJECTS 192

Key Phase I and preclinical compounds in neuropathic pain 193

Selective sodium channel blockers 196

Vanilloid TRPV1 antagonists 197

Preclinical trial data 197

NGX-1998 198

GRC-6211 198

SAR-115740 198

N-type calcium channel blockers 198

Spinal cord and peripheral nerve stimulation 199

BIBLIOGRAPHY 200

Journals 200

Websites 206

Datamonitor reports 216

APPENDIX A 218

Methodology 218

Datamonitor forecast methodology 218

ICD-10 codes 218

Product forecasts 219

Definition of a standard unit 220

Datamonitor drug assessment summary 221

Contributing experts 222

Biographies 222

APPENDIX B 224

About Datamonitor 224

About Datamonitor Healthcare 224

Datamonitor Healthcare's therapy area capabilities 225

About the Disease analysis team 226

Disclaimer 227

List of Tables

Table 1: Neuropathic pain market size across the seven major markets ($m), 2007 and 2017 6

Table 2: Sales forecasts ($m) of key pipeline products in neuropathic pain, 2007-2017 8

Table 3: Abbreviations for neuropathic pain subtypes 14

Table 4: Diabetic neuropathic pain patient populations across the seven major markets, 2008 20

Table 5: Post-herpetic neuralgia patient population across the seven major markets, 2008 21

Table 6: HIV neuropathic pain patient population across the seven major markets, 2008 22

Figure 7: Key unmet needs in neuropathic pain, 2008 29

Table 7: Recommended core outcomes measures for clinical trials of chronic pain treatment efficacy 34

Table 8: Forecast launch dates for neuropathic pain drugs in the US and 5EU, 2008-2012 62

Table 9: Forecast launch dates for neuropathic pain drugs in Japan, 2010-2012 62

Table 10: Pivotal patent expiries for key marketed neuropathic pain drugs in the US and 5EU, 2012-16 63

Table 11: Neuropathic pain market sub-type definition by ICD-10 codes 71

Table 12: Number of key neuropathic pain drugs by class and phase of development, 2008 74

Table 13: Phase II & III R&D pipeline for neuropathic pain, 2008 80

Table 14: Key glutamate receptor modulators in the late-stage R&D pipeline for neuropathic pain, 2008 100

Table 15: Lyrica: key facts 105

Table 16: Estimated key events, approvals and launch dates impacting Zenvia's revenue forecast, 2008-2017 109

Table 17: Estimated key events, approvals and launch dates impacting NP-1's revenue forecast, 2008-2017 116

Table 18: Key ion channel modulators in the late-stage R&D pipeline for neuropathic pain, 2008 130

Table 19: Estimated key events, approvals and launch dates impacting Vimpat's revenue forecast, 2008-2017 134

Table 20: Estimated key events, approvals and launch dates impacting ralfinamide's revenue forecast, 2008-2017 143

Table 21: Key GABA modulators in the late-stage R&D pipeline for neuropathic pain, 2008 152

Table 22: Estimated key events, approvals and launch dates impacting XP13512's revenue forecast, 2008-2017 157

Table 23: Other drugs in late-stage R&D pipeline for neuropathic pain, 2008 167

Table 24: Estimated key events, approvals and launch dates impacting Transacin's revenue forecast, 2008-2017 172

Table 25: Key drugs in Phase I development for neuropathic pain, 2008 193

Table 26: Key drugs in preclinical development for neuropathic pain, 2008 194

Table 27: Neuropathic pain market definition by ICD-10 codes 218

Table 28: Datamonitor drug assessment parameters 221

List of Figures

Figure 1: Forecast of the neuropathic pain market value across the seven major markets, 2008-2017 7

Figure 2: Key neuropathic pain pipeline drug historical sales and forecasts, 2004-2017 9

Figure 3: Datamonitor drug assessment summary of pipeline therapies in development for neuropathic pain, 2008 10

Figure 4: Sales of molecules for neuropathic pain ($m), 2007 23

Figure 5: Total neuropathic pain sales across the seven major markets by region, 2004-07 27

Figure 6: Total neuropathic pain sales in the six major markets($m), 2007 28

Figure 8: Historical and forecast neuropathic pain-specific sales revenue for key brand and pipeline drugs across the seven major markets, 2004-2017 42

Figure 9: Sales forecast for Lyrica in neuropathic pain across the seven major markets to 2017 43

Figure 10: Lyrica SWOT analysis 44

Figure 11: Datamonitor's competitive positioning analysis of Lyrica, 2008 45

Figure 12: Historical and forecast sales for Neurontin in neuropathic pain across the seven major markets, 2004-2017 49

Figure 13: Neurontin SWOT analysis 50

Figure 14: Historical and forecast sales for Lidoderm in neuropathic pain across the seven major markets, 2004-2017 52

Figure 15: Lidoderm SWOT analysis 53

Figure 16: Sales forecast for Cymbalta in neuropathic pain across the seven major markets, 2004-2017 56

Figure 17: Cymbalta SWOT analysis 57

Figure 18: Tegretol SWOT analysis 59

Figure 19: Impact of each key event on the neuropathic pain market across the seven major markets, 2008-2017 61

Figure 20: Population of neuropathic pain subtypes in the seven major markets, 2008 69

Figure 21: Percentage neuropathic pain sales by subtype, 2008 70

Figure 22: Drugs in development for neuropathic pain by class and development stage, 2008 73

Figure 23: Pfizer sales by therapeutic area 2006 85

Figure 24: Sales of Neurontin, gabapentin and Lyrica for neuropathic pain ($m), 2003-07 86

Figure 25: Historical sales of Lyrica, Neurontin, Cymbalta and generic gabapentin, 2003-07 87

Figure 26: Pfizer's Lyrica and CNS sales 2004-07 ($ billion) 88

Figure 27: Eli Lilly sales by therapeutic area, 2006 89

Figure 28: Cymbalta neuropathic pain specific sales in the seven major markets, 2003-07 ($m) 90

Figure 29: UCB sales by therapeutic area, 2007 91

Figure 30: Datamonitor drug assessment summary of key glutamate receptor modulators in development for neuropathic pain, 2008 101

Figure 31: Sales forecasts for glutamate receptor modulators in neuropathic pain across the seven major markets, 2008-2017 102

Figure 32: Sales forecast for Zenvia in neuropathic pain across the seven major markets, 2009-2017 108

Figure 33: Datamonitor's competitive positioning analysis of Zenvia, 2008 110

Figure 34: Sales forecast for NP-1 in neuropathic pain across the seven major markets, 2008-2017 115

Figure 35: Datamonitor's competitive positioning analysis of NP-1, 2008 117

Figure 36: Datamonitor drug assessment summary of pipeline ion channel modulators in development for neuropathic pain, 2008 131

Figure 37: Sales forecasts for ion channel modulators in neuropathic pain across the seven major markets, 2008-2017 132

Figure 38: Sales forecast for Vimpat in neuropathic pain across the seven major markets, 2008-2017 133

Figure 39: Datamonitor's competitive positioning analysis of Vimpat in neuropathic pain, 2008 135

Figure 40: Sales forecast for ralfinamide in neuropathic pain across the seven major markets, 2010-2017 142

Figure 41: Datamonitor's competitive positioning analysis of ralfinamide in neuropathic pain, 2008 144

Figure 42: Datamonitor drug assessment summary of pipeline GABA receptor modulators in development for neuropathic pain, 2008 153

Figure 43: Sales forecasts for GABA modulators in neuropathic pain across the seven major markets, 2008-2017 154

Figure 44: Sales forecast for XP13512 in neuropathic pain across the seven major markets, 2008-2017 156

Figure 45: Datamonitor's competitive positioning analysis of XP13512, 2008 158

Figure 46: Sales forecast for Gabapentin GR in neuropathic pain across the seven major markets, 2009-2017 162

Figure 47: Datamonitor's competitive positioning analysis of Gabapentin GR, 2008 163

Figure 48: Datamonitor drug assessment summary other therapies in development for neuropathic pain, 2008 168

Figure 49: Sales forecasts for 'Other' drugs in neuropathic pain across the seven major markets, 2008-2017 169

Figure 50: Sales forecast for Transacin in neuropathic pain across the seven major markets, 2008-2017 171

Figure 51: Datamonitor's competitive positioning analysis of Transacin in neuropathic pain, 2008 173

Figure 52: Datamonitor drug assessment summary of neuropathic pain treatments, 2007 222

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