Contents:

CHAPTER 1 EXECUTIVE SUMMARY 3 Objective of the analysis 3 Our insight into the osteoporosis and HRT market 3 CHAPTER 2 MARKET DEFINITION AND OVERVIEW 10 Market definition for this report 10 Current market situation 11 Strategic scope and focus 14 Epidemiology of osteoporosis 14 Methodological difficulties in assessing prevalence 15 Prevalence of osteoporosis and osteopenia in postmenopausal women 16 Overview of the prevalence of osteoporosis and osteopenia in postmenopausal women 17 US 19 Japan 20 France 21 Germany 21 Italy 22 Spain 22 UK 23 Segmentation of osteoporosis 23 Prevalence of osteoporosis and osteopenia in men 24 Introduction 24 Overview of the prevalence of osteoporosis/osteopenia in men 24 US 26 Japan 27 France 27 Germany 28 Spain 28 UK 29 CHAPTER 3 COUNTRY MARKET ASSESSMENTS 30 Current and future opportunities and threats in the osteoporosis and HRT market 30 Global opportunities and threats 30 Opportunities 30 US: opportunities and threats 31 Opportunities 31 Threats 32 Japan: opportunities and threats 33 Opportunities 33 Threats 33 France: opportunities and threats 35 Opportunities 35 Italy: opportunities and threats 35 Opportunities 35 Threats 36 UK: opportunities and threats 38 Opportunities 38 Threats 38 CHAPTER 4 FORECAST ANALYSIS 41 Assumptions and events 41 Bisphosphonates 41 Fosamax 41 Actonel 44 Pipeline bisphosphonates 45 SERMs 47 Evista 47 Calcitonins 49 Miacalcin 49 Pipeline calcitonins 50 Parathyroid hormone derivatives 51 Forteo 51 Pipeline PTH therapy 52 Hormone therapy 52 Marketed products 52 Limitations of data 53 Forecasts 54 CHAPTER 5 COMMERCIAL IMPACT AND LIFECYCLE MANAGEMENT: CASE STUDIES 55 Introduction 55 Case studies 55 Wyeth HRT portfolio strategy – preserving the Premarin brand and gambling on new molecules 55 Premarin/Prempro 55 Bazedoxifene and trimegestone 59 NPS pre-launch strategy for Preos – piggybacking Kineret detailing activity 60 Chugai cornering the Japanese market 61 Merck’s Fosamax launch activity 61 Heavy Phase IV activity among top three drugs 63 Combination trials with Forteo, Evista and Fosamax 66 Impact of the WHI on non-hormonal osteoporosis drugs 67 APPENDIX A – MARKET DATA AND MAJOR BRAND KEY FACTS 71 Bisphosphonates market data 71 SERMs market data 72 Calcitonins market data 72 PTH market data 73 APPENDIX B 74 Bibliography 74 Epidemiology 74 Clinical trial data 74 Report methodology 74

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Page 39...... - no bisphosphonate treatment to be prescribed to postmenopausal women with osteoporosis who have not suffered a fracture; - bisphosphonates only to be prescribed for postmenopausal women aged 65 years and older if they have a fracture with no need for DXA; - bisphosphonate treatment for younger women with a fracture will also need to have very low BMD T-score confirmed by DXA below -3.2 SD or low BMD (T-score -2.5 SD) and a history of maternal hip fracture; - teriparatide only to be prescribed for women over 70 years with multiple fragility fractures who have not responded adequately to bisphosphonates and have a T-score below -4.0 SD or a history of maternal hip fracture; - raloxifene is not recommended for the treatment of postmenopausal osteoporosis. These measures, if enforced, would restrict the choice of drugs available to treat osteoporosis as well as limit access to those patients who have already suffered a fracture, leaving those patients without fracture untreated and at greater risk. This is despite the fact that the cost of treating osteoporotic fractures in England and Wales is estimated to reach £2.0 billion by 2010. Given the recent large-scale HRT trials carried out in the US and the UK and the resulting updated guidelines for hormone therapy, the NICE proposals could leave thousands of women who are at risk of fracture, unprotected. HRT is no longer recommended to prevent and treat osteoporosis and the consideration of non-hormonal alternatives for treatment is advised. However, younger postmenopausal women in particular could have even those alternatives removed. Heavy criticism, led by the NOS, in response to the draft guidelines during the consultation period included mobilizing the public to write to their MPs expressing their concerns over the implications of the proposal. This resulted in a parliamentary debate in the House of Commons on March 3, 2004 where NICE announced that it will reconsider its plans for the treatment of osteoporosis. Part of this reassessment involved dividing the appraisal into two parts, published separately. One of these will address primary prevention of osteoporotic fractures and the other will focus on secondary prevention. In July 2004, the final NICE appraisal document on these two issues was issued. Key changes included the maintenance of choice of effective treatment for postmenopausal women with osteoporotic fractures. However, there remains a lack of provision for women under 65 years who also have fragility fractures. The NOS plans