Introduction
 
The neuropathic pain market has traditionally been a poorly defined area, with widely varying drug classes prescribed. With many drugs now in clinical trials for key neuropathic pain sub-types, pharma companies with powerful marketing arms are expected to bring attention to this potentially lucrative market and its considerable unmet needs.
 

 
Scope
 
Overview of patient potential, segmentation by indication and unmet needs in neuropathic pain across the seven major markets
 
Detailed pipeline analysis for key products in each indication, plus drug sales forecasts to 2014 and clinical trial information
 
Commercial and clinical attractiveness of late Phase compounds likely to be launched in a neuropathic pain indication
 
Investigation of the key neuropathic pain subtypes: post-herpetic neuralgia, diabetic neuropathic pain and HIV associated neuropathic pain
 
Highlights
 
Gabapentin remains the gold standard treatment to beat in the 5 EU and US neuropathic pain markets, which are estimated at a combined total of $2,543m in 2005, reaching $4,118m in 2007. However, Japan offers a significantly different market, based on NSAIDs and nerve blockers, and would be a good opportunity for new treatments in neuropathic pain.
 

 
The mode of drug delivery has important implications on the ease of drug administration and patient compliance, a key issue in a market where the gold standard has a dosing profile of up to four tablets per day. 20% of the products launched in the forecast are reformulations, with more due to emerge through early Phase trials.
 

 
Pfizer's GABA modulator franchise appears safe, and half the brand value of Lyrica (pregabalin) is estimated to be for neuropathic pain. Only Lilly's new antidepressant, Cymbalta (duloxetine) is forecast to compete, but cheaper generic gabapentin offers significant competition to all novel products launching at a premium brand price.
 

 
Reasons to Purchase
 
Understand key market drivers and predict the future performance of key compounds
 
Quantify the future size and scope of market and potential for novel molecular-targeted treatments in neuropathic pain
 
Benchmark pipeline agents against currently marketed products and market needs

TABLE OF CONTENTS
 
CHAPTER 1 EXECUTIVE SUMMARY 3
 
Scope of the analysis 3
 
Datamonitor insight into the neuropathic pain market 4
 
Summary 4
 
Datamonitor Pipeline Assessment Summary 5
 
CHAPTER 2 PATIENT POTENTIAL 17
 
Definition of neuropathic pain 17
 
Segmentation of neuropathic pain is key to clinical trial design 18
 
General neuropathic pain provides a broader customer base in the EU 18
 
US approval requires evidence in each neuropathic pain subtype 18
 
Diabetic neuropathic pain 20
 
Post-herpetic neuralgia 22
 
HIV neuropathic pain 22
 
Neuropathic low-back pain 23
 
Other subtypes 24
 
Unmet needs in neuropathic pain are greater than current met clinical needs 24
 
Current drugs only show a maximum of 50% pain reduction, but latest treatments are comparatively safe 25
 
Generic gabapentin introduces cost competition in most markets 26
 
Pharma companies push for a mechanism-based approach 27
 
Dosing and administration methods are a key area where new treatments can easily compete with the gold standard 28
 
CHAPTER 3 R&D APPROACH 29
 
Classification of pipeline products 29
 
NMDA receptor antagonists 29
 
Ion channel modulators 29
 
GABA modulators 30
 
Others 30
 
Gabapentin is still the gold-standard neuropathic pain therapy 32
 
Choice of endpoint is the key clinical trial design factor in neuropathic pain 39
 
Clinical trial endpoints in neuropathic pain 40
 
50% reduction in pain is a primary measure of efficacy, but choice of pain scale can dramatically affect its achievement 42
 
Multiple pain and Quality of Life assessment questionnaires should be used in trials 43
 
Side effects differentiate pipeline treatments 47
 
Length of trial should indicate titration period for physician ease of use 47
 
CHAPTER 4 NEUROPATHIC PAIN MARKET DEFINITION 48
 
Five treatments are currently marketed for neuropathic pain 48
 
Majority of other treatments included in the market are anticonvulsants 49
 
The market value is calculated using IMS diagnosis value 51
 
Japan uses NSAIDs and nerve blockers for neuropathic pain treatment 52
 
Forecast caveats 53
 
CHAPTER 5 NEUROPATHIC PAIN PIPELINE ANALYSIS 55
 
Pipeline overview 55
 
Phase III and above overview 57
 
Phase II overview 58
 
Phase I overview 59
 
Preclinical overview 60
 
Key companies involved in the neuropathic pain pipeline 63
 
Pfizer’s CNS portfolio has internal competition, but the company is still expected to lead in neuropathic pain 63
 
Lyrica: a future blockbuster 64
 
Neuropathic pain: the “chance” indication? 64
 
Strategies for success 65
 
Drug delivery formulations and reformulations bulk up the pipeline with a daily or less oral treatment as the goal 65
 
Oral delivery formulations 65
 
Intravenous delivery formulations 66
 
Transdermal delivery formulations 66
 
Topical formulations 67
 
Low drug-drug interactions are key for physicians treating HIV and diabetic patients on drug cocktails 67
 
High quality marketing and careful indication selection set pipeline leaders apart 67
 
Future mechanism research could revolutionize neuropathic pain treatment 68
 
Opportunities and threats in the neuropathic pain market 69
 
Pipeline assessment methodology 71
 
CHAPTER 6 NMDA RECEPTOR ANTAGONISTS LATE-STAGE DRUG ANALYSIS & FORECASTS 72
 
Comparison of key compounds in NMDA receptor antagonists 73
 
Neurodex (AVP-923) 74
 
Drug overview 74
 
Clinical trial data 75
 
Neurodex is being investigated in many indications increasing patient potential 76
 
A neuropathic pain indication is not priority for Neurodex 76
 
Dosing is the only unmet need to show a competitive advantage for Neurodex 76
 
Neurodex forecasts to 2014 78
 
NP-1 80
 
Drug overview 80
 
Clinical trial data 80
 
Topical administration increases potential uses for NP-1 81
 
EpiCept searches for a marketing partner 81
 
Promising initial results but synergistic effect and mechanism clarification required 82
 
NP-1 forecast 83
 
Traxoprodil 84
 
Drug overview 84
 
Clinical trial data 85
 
Little known Gracely pain scale may provide more differentiated efficacy results 86
 
Neuropathic pain unlikely to be primary launch indication as Pfizer focuses on stroke while avoiding intra-company product competition 86
 
Pointers for a good side-effect profile and efficacy may lead to off-label use on launch in stroke indication 87
 
Traxoprodil forecast 88
 
Memantine 89
 
Drug overview 89
 
Clinical trial data 89
 
FDA committee have “concerns” over memantine approval in Alzheimer’s 90
 
Numerous licensing agreements result in the development of memantine molecule in many areas, but none with significant success 90
 
Continued disappointing clinical data points to delay in memantine NDA submission from Forest 91
 
Memantine forecasts 91
 
Other NMDA receptor antagonists 91
 
CNS-5161 91
 
Perzinfotel 92
 
CHAPTER 7 ION CHANNEL MODULATORS LATE-STAGE DRUG ANALYSIS AND FORECASTS 93
 
Comparison of key compounds in ion channel modulators 93
 
Pregabalin 95
 
Drug overview 95
 
Clinical trial data 95
 
Pregabalin shows promise in anxiety and epilepsy and may need to increase profile in neuropathic pain 98
 
Pfizer’s resources convince FDA of cancer safety 98
 
Improvement in dosing and side-effect profile make pregabalin one of the most promising pipeline candidates 98
 
Pregabalin forecasts to 2014 99
 
Ralfinamide 102
 
Drug overview 102
 
Clinical trial data 102
 
Selective approach will reduce brand patient potential but will greatly boost use in neuropathic pain for ralfinamide 103
 
Collaboration and recent fundraising efforts will allow continued development 104
 
Selectivity of ralfinamide may reduce side effects but only larger trials will tell 104
 
Success across neuropathic pain indications points towards mechanistic approach 104
 
Ralfinamide forecasts to 2014 105
 
Lamictal XR 108
 
Drug overview 108
 
Clinical trial data 108
 
Off-label use of Lamictal predicts high acceptance of once-daily neuropathic pain approved version 110
 
GSK fights original formulation patent expiry with both new indication and formulation approvals 110
 
Skin rash side effect main threat to Lamictal XR uptake 110
 
Lamictal XR forecast to 2014 111
 
Lacosamide 114
 
Drug overview 114
 
Clinical trial data 114
 
Lacosamide will also treat epilepsy, following well-known path for neuropathic pain treatments 115
 
Despite less general global presence Schwarz looks set to increase presence in the CNS market 115
 
Evidence of low-drug interaction will add to physician confidence in lacosamide 116
 
Lacosamide forecasts to 2014 117
 
Tiagabine 118
 
Drug overview 118
 
Clinical trial data 119
 
FDA seizure warning severely threatens tiagabine’s patient potential 119
 
Current marketing infrastructure for this molecule may help overcome FDA warning for tiagabine 120
 
Promising results in a small trial must be replicated on a larger scale to prove efficacy 120
 
Tiagabine forecast to 2014 121
 
XP13512 124
 
Drug overview 124
 
Clinical data 124
 
Restless leg syndrome indication offers large sales for this molecule 126
 
XP13512 will be highly successful in the neuropathic pain market if this new gabapentin dosing mechanism continues to produce results 126
 
XP13512 forecast to 2014 127
 
Other Ion channel modulators 129
 
Gabapentin GR 129
 
CHAPTER 8 OTHERS LATE-STAGE DRUG ANALYSIS AND FORECASTS 130
 
Comparison of key other drugs 130
 
Duloxetine 132
 
Drug overview 132
 
Clinical trial data 132
 
Treatment of comorbid depression with duloxetine will appeal to prescribers 134
 
Eli Lilly’s CNS dominance will boost marketing potential but competition from Effexor may reduce uptake 134
 
Duloxetine improves on older marketed treatments’ side-effect profile 135
 
Duloxetine forecasts to 2014 137
 
NGX-4010 139
 
Drug overview 139
 
Clinical trial data 140
 
NGX-4010 will battle against cheap generic competition in the form of capsaicin creams 141
 
NeurogesX is successfully raising funds to continue development, but will require more marketing expertise to launch this product 142
 
Duration of efficacy offers an advantage over existing topical treatments, but the mechanism is still in doubt 142
 
NGX-4010 forecasts to 2014 143
 
Sativex (SAB-378) 147
 
Drug overview 147
 
Clinical trial data 147
 
Uses for Sativex are wide reaching but political/social factors are likely to prevent the achievement of this potential 148
 
Bayer’s marketing experience will greatly improve Sativex uptake 148
 
Abuse potential is high but evidence of some efficacy in many neuropathic pain subtypes may counteract this 149
 
Sativex forecasts to 2014 150
 
Devazepide 152
 
Drug overview 152
 
Clinical data 152
 
A significant efficacy will be required by devazepide to compete with opioids 153
 
2002 data shows the ML Labs/Panos partnership is looking to increase this molecule’s profile 153
 
Novel mechanism requires further investigation and company backing before the true potential can be assessed 153
 
Devazepide forecast 153
 
Other drugs 154
 
Effexor 154
 
DA-5018 155
 
KDS-2000 155
 
HP-184 155
 
Prosaptide 156
 
CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS 157
 
Key Phase I and preclinical compounds in neuropathic pain 157
 
Using gene therapy for nerve regeneration 158
 
TNF inhibitors in neuropathic pain 160
 
Renovis trial data 160
 
APPENDIX A 162
 
Methodology 162
 
Datamonitor forecast methodology 162
 
Sales calculations 164
 
Datamonitor drug assessment summary 165
 
Contributing experts 167
 
Bibliography 167
 
Websites 175
 
APPENDIX B 177
 
About Datamonitor 177
 
About Datamonitor Healthcare 177
 
Datamonitor Healthcare’s therapy area capabilities 178
 
About the CNS, Arthritis and Pain analysis team 179
 
Disclaimer 181