Contents:

CHAPTER 1 Executive summary 3 1.1 Scope of the Analysis 3 1.2 Insight into diabetic neuropathic pain 3 DNP is a relatively common affliction occurring in advanced diabetes patients. Patients with DNP are often referred to neurologists or pain specialists for treatment, where they are likely given gabapentin and/or amitriptyline. However, as these treatments often only provide marginal relief of DNP symptoms, there remains a need for improved long-term pain management. 4 With the launch of pregabalin in 2004, Pfizer will effectively retain much of its market share when gabapentin finally loses US patent protection. Approval for DNP in the US will be a major advantage in the increasingly competitive neuropathic pain market as currently there are no drugs licensed for this indication. The niche market will also be impacted by the off-label use and potential launch of various other products for DNP and diabetic neuropathy. 5 Over the coming years, top-tier CNS players, such as Pfizer, GSK, and Lilly, will dominate the DNP market. To avoid direct competition with these large players, Datamonitor recommends smaller companies aiming to enter the lucrative neuropathic pain arena establish their products in other, less common neuropathic pain subtypes, such as HIV associated neuropathic pain. 7 1.3 Diabetic Neuropathic Pain Insight: methodology 8 CHAPTER 2 Introduction 9 CHAPTER 3 Patient Potential 9 3.1 Definition and classification of diabetic neuropathy 9 Sensorimotor Neuropathy 9 Cardiovascular Autonomic Neuropathy 9 Gastrointestinal Autonomic Neuropathy 9 Genitourinary Autonomic Neuropathy 9 3.2 Epidemiology across the seven major markets 9 Prevalence 9 Breakdown by severity 9 CHAPTER 4 Assessment and treatment 9 4.1 Referral patterns 9 Overview 9 US 9 Japan 9 France 9 Germany 9 Italy 9 Spain 9 UK 9 4.2 Importance of therapeutic endpoints in diabetic neuropathic pain on prescribing decisions 9 Overview 9 US 9 Japan 9 France 9 Germany 9 Italy 9 Spain 9 UK 9 4.3 Pharmacotherapy 9 Introduction 9 Aldose reductase inhibitors 9 Antidepressants 9 Tricyclic antidepressants 9 Selective serotonin-reuptake inhibitors 9 Other antidepressants 9 Anticonvulsants 9 Opioids 9 Other drugs 9 Non-steroidal anti-inflammatory drugs 9 Antiarrhythmics 9 NMDA antagonists 9 Topical agents 9 Alternative therapies 9 4.4 Treatment of diabetic neuropathic pain in the seven major markets 9 Overview of commonly used drugs 9 Gabapentin 9 Amitriptyline 9 Lidocaine patch 9 NSAIDS 9 Mexiletine 9 Epalrestat 9 Alpha-lipoic acid 9 Summary 9 US 9 Summary of diabetic neuropathic pain treatment in the US 9 First-line therapy 9 Second-line therapy 9 Third-line therapy 9 Japan 9 Summary of diabetic neuropathic pain treatment in Japan 9 First-line therapy 9 Second-line therapy 9 Third-line therapy 9 France 9 Summary of diabetic neuropathic pain treatment in France 9 First-line therapy 9 Second-line therapy 9 Third-line therapy 9 Germany 9 Summary of diabetic neuropathic pain treatment in Germany 9 First-line therapy 9 Second-line therapy 9 Third-line therapy 9 Italy 9 Summary of diabetic neuropathic pain treatment in Italy 9 First-line therapy 9 Second-line therapy 9 Third-line therapy 9 Spain 9 Summary of diabetic neuropathic pain treatment in Spain 9 First-line therapy 9 Second-line therapy 9 Third-line therapy 9 UK 9 Summary of diabetic neuropathic pain treatment in the UK 9 First-line therapy 9 Second-line therapy 9 Third-line therapy 9 4.5 R&D drugs 9 Pipeline overview 9 Protein Kinase C Inhibitors 9 Ruboxistaurin 9 Aldose reductase inhibitors 9 Fidarestat 9 AS-3201 9 Anticonvulsants 9 Pregabalin 9 Topiramate 9 Lamotrigine 9 Levetiracetam 9 Antidepressants 9 Duloxetine 9 NMDA antagonists 9 Memantine 9 AVP-923 9 4.6 Unmet needs 9 Disease modifying agents 9 More-effective pain control 9 Prevention of neuropathic foot ulcers 9 Better understanding of DNP pathophysiology 9 CHAPTER 5 Appendix A 9 5.1 Bibliography 9 References 9 Websites 9 5.2 Contributing experts 9 Professor John D Loeser MD 9 Professor Kazuo Hanaokam MD 9 Professor Cesare Fieschi MD 9 Professor Henry J McQuay MD 9 Professor Praveen Anand MD 9 Professor Shuji Dohi MD 9 Professor Andreas Straube MD 9 Professor Giorgio Sandrini MD 9 Assistant Professor Brian D Loftus MD 9 Associate Professor Barth L Wilsey MD 9 Dr Gockel MD 9 Dr Gary J McCleane MD 9 Dr Philippe Poulain MD 9 Dr Ricardo Ruiz-Lopez MD 9 Dr Charles H Ripp MD 9 Dr David Bowsher MD 9 Dr Justin C Riutta MD 9 Dr Derek Enlander MD 9 Dr Delong MD 9 Dr Ducloux MD 9 Professor Vignon MD 9 Professor Lauren Shaiova MD 9 Professor Donald I Abrams MD 9 Dr Nicola E Mackie MD 9 5.3 Physician research methodology 9 Introduction 9 Our research partners 9 Research objectives 9 Questionnaire development 9 Research methodology 9 Data processing 9 Quality control 9 5.4 Neuropathic Pain Insight Questionnaire 9 CHAPTER 6 Appendix B 9 Research and analysis methodologies 9 6.2 About the CNS analysis team 9 Key therapy team members 9 Lynda Lynch, Director CNS 9 David Abramson, Therapeutic Lead Consultant 9 About the Author 9 Ben Greener, Senior CNS Analyst 9