Contents:

TABLE OF CONTENTS About Datamonitor healthcare 2 About the CNS pharmaceutical analysis team 2 CHAPTER 1 Executive summary 3 1.1 Scope of the analysis 3 1.2 Datamonitor insight into fibromyalgia 3 Fibromyalgia is a common syndrome that is substantially under served by the medical profession and the pharmaceutical industry. The challenge facing investors is to provide improved understanding of the biologic and physiologic processes responsible for the symptoms, in order to develop better pain medications that can improve quality of life 4 The popularity of amitriptyline among physicians for treating fibromyalgia has paved the way for the uptake of newer antidepressants. The biggest commercial opportunity is for manufacturers of serotonin and noradrenaline reuptake inhibitors (SNRIs). Forest’s SNRI milnacipran is the closest to entering the market, although competition from Eli Lilly and Wyeth can be expected in the near future 5 Datamonitor recommends companies aiming to enter the fibromyalgia market push regulatory agencies to recognize the condition as a single clinical entity. Until this is achieved, companies will be unable to gain labeling for fibromyalgia 6 1.3 Fibromyalgia Insight: methodology 7 CHAPTER 2 Introduction 16 CHAPTER 3 Patient potential 17 3.1 Definition of fibromyalgia 17 3.2 Epidemiology across the seven major markets 18 Prevalence 18 Breakdown by severity 19 CHAPTER 4 Assessment and treatment 24 4.1 Diagnosis 24 4.2 Referral patterns 26 Overview 26 US 27 Japan 27 France 28 Germany 29 Italy 30 Spain 31 UK 33 4.3 Importance of therapeutic endpoints in fibromyalgia on prescribing decisions 34 Overview 34 US 35 Japan 36 France 37 Germany 38 Italy 39 Spain 39 UK 40 4.4 Pharmacotherapy 41 Introduction 41 4.5 Treatment of fibromyalgia in the seven major markets 42 Overview 42 Amitriptyline 42 Venlafaxine 42 Other antidepressants 43 Gabapentin 44 Tramadol 44 NSAIDs 45 Datamonitor summary 45 US 46 Summary of fibromyalgia treatment in the US 46 First-line therapy 48 Second-line therapy 48 Third-line therapy 50 Japan 51 Summary of fibromyalgia treatment in Japan 51 First-line therapy 52 Second-line therapy 52 Third-line therapy 53 France 54 Summary of fibromyalgia treatment in France 54 First-line therapy 56 Second-line therapy 58 Third-line therapy 59 Germany 60 Summary of fibromyalgia treatment in Germany 60 First-line therapy 61 Second-line therapy 62 Third-line therapy 63 Italy 64 Summary of fibromyalgia treatment in Italy 64 First-line therapy 65 Second-line therapy 66 Third-line therapy 68 Spain 69 Summary of fibromyalgia treatment in Spain 69 First-line therapy 70 Second-line therapy 71 Third-line therapy 72 UK 73 Summary of fibromyalgia treatment in the UK 73 First-line therapy 73 Second-line therapy 75 Third-line therapy 76 4.6 R&D drugs 77 Pipeline overview 77 Milnacipran 78 Duloxetine 78 Venlafaxine 79 Pregabalin 80 4.7 Unmet needs 81 CHAPTER 5 Appendix A 83 5.1 Bibliography 83 References 83 Websites 87 5.2 Contributing experts 88 Professor John D Loeser MD 88 Professor Kazuo Hanaokam MD 88 Professor Cesare Fieschi MD 88 Professor Henry J McQuay MD 88 Professor Praveen Anand MD 88 Professor Shuji Dohi MD 89 Professor Andreas Straube MD 89 Professor Giorgio Sandrini MD 89 Assistant Professor Brian D Loftus MD 89 Associate Professor Barth L Wilsey MD 89 Dr Gockel MD 89 Dr Gary J McCleane MD 89 Dr Philippe Poulain MD 89 Dr Ricardo Ruiz-Lopez MD 90 Dr Charles H Ripp MD 90 Dr David Bowsher MD 90 Dr Justin C Riutta MD 90 Dr Derek Enlander MD 90 Dr Delong MD 90 Dr Ducloux MD 90 Professor Vignon MD 90 Professor Lauren Shaiova MD 91 Professor Donald I Abrams MD 91 Dr Nicola E Mackie MD 91 5.3 Physician research methodology 91 Introduction 91 Our research partners 93 Research objectives 94 Questionnaire development 96 Research methodology 96 Data processing 99 Quality control 99 5.4 Neuropathic Pain Insight Questionnaire 99 CHAPTER 6 Appendix B 106 6.1 About Datamonitor 106 About Datamonitor Healthcare 106 Datamonitor Healthcare’s research and analysis methodologies 107 6.2 Datamonitor Healthcare’s therapy area capabilities 107 About the CNS analysis team 108 Datamonitor Healthcare’s Consulting expertise 109 Datamonitor’s Therapeutic Consulting expertise 110 Key therapy team members 110 Lynda Lynch, Director CNS 110 David Abramson, Therapeutic Lead Consultant 111 About the Author 111 Ben Greener, Senior CNS Analyst. 111 Disclaimer 113