Commercial and Pipeline Insight - Hepatitis B

ABOUT DATAMONITOR HEALTHCARE 2
About the Infectious Diseases pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Objective of the analysis 3
Datamonitor insight into the disease market 3
Contributing experts 5
Key metrics 6
Datamonitor Pipeline Assessment Summary 7
Related reports 8
Upcoming related reports 8
CHAPTER 2 HEPATITIS B - DISEASE BACKGROUND 9
Summary 9
Epidemiology 9
Virus 13
Structure 13
Lifecycle 14
Transmission 16
Risk groups 17
Symptoms and disease progression 18
Acute HBV infection 19
Chronic HBV infection 21
Diagnosis 24
CHAPTER 3 MARKET DEFINITION AND OVERVIEW 27
Summary 27
Market definition for this report 28
Current market situation 29
Sales and volume use in HBV are increasing steadily 29
Key events - Five new drug approvals since 1999 have increased treatment diversity 31
Country market analysis - US is leading the field, while market growth is strongest in the EU5 32
US: New antivirals experience a good uptake in a diverse market 33
Japan: Lamivudine takes over from interferon alfa-2b 34
EU5: Strong growth driven by adefovir 36
Market drivers and restrictors - Disease awareness as the key factor 38
Lack of awareness leads to low diagnosis and treatment rates for HBV infections 39
Segmentation of Hepatitis B 42
HBV prevalence is highest in adults aged >25 years of age 42
Men represent a higher percentage of HBV patients than women 43
Sex between men accounts for an increasing percentage of HBV cases 44
Immigrants account for the vast majority of infections 45
HIV-HBV co-infected patients constitute a significant target population 47
Unmet needs in hepatitis B 47
A cure for hepatitis B is the key clinical unmet need 48
The increasing level of HBV drug resistance is creating a need for novel therapeutics 48
Combination therapy approaches are needed for second- and third-line therapy 49
Market forecast 49
The HBV market is set to grow to $1.2 billion by 2012, but will stagnate afterwards 49
Genericization will start in 2010, but its impact will remain limited 50
The US will remain leader in sales, whereas Japan will show high growth in volume use 51
CHAPTER 4 PREVENTION AND TREATMENT 53
Summary 53
Vaccines 54
HBV vaccination is recommended in more and more countries 54
Plasma-derived vaccines have been replaced by safer, recombinant products 56
Currently available vaccines provide strong protection 57
HBV vaccination is widely regarded as safe 57
Coverage in most of the 7MM is high 58
Currently marketed Hep B vaccines include single-antigen as well as combination vaccines 59
HBV pharmacotherapy 60
Serum levels of ALT and HBV DNA are the key factors for treatment initiation 63
Suppression of HBV replication is the key endpoint in chronic hepatitis B (CHB) therapy 63
Currently marketed drugs are split into interferons and antivirals 65
Choice of first-line treatment depends on multiple factors 67
Interferons 71
Antivirals 82
CHAPTER 5 KEY PLAYERS IN THE HEPATITIS B MARKET 104
Summary 104
Gilead and Bristol-Myers Squibb will dominate the HBV market, whereas GSK and Schering-Plough will lose share 105
GSK - vaccines as future revenue drivers? 108
Current position 108
Strategic development 110
Outlook 111
Gilead - New hope in tenofovir 111
Current position 111
Strategic development 112
Outlook 113
Bristol-Myers Squibb - the one-product franchise 114
Current position 114
Strategic development 114
Outlook 115
Novartis - a new entrant with ambitions 116
Current position 116
Strategic development 116
Outlook 117
Roche - flying on the wings of Pegasys 118
Current position 118
Strategic development 118
Outlook 118
Schering-Plough - gloomy prospects 119
Current position 119
Strategic development 119
Outlook 119
CHAPTER 6 FORECASTING ANALYSIS 120
New product launches 120
Patent expiries 121
Data definitions, limitations and assumptions 122
Standard units 122
Japanese market data 122
Forecasts 122
Forecast methodology 122
CHAPTER 7 HBV PIPELINE: CLASS OVERVIEW AND R&D APPROACH 123
Summary 123
Pipeline overview: The immune system is the key target for future HBV drugs 123
Clinical trial design in hepatitis B 125
Vaccines 125
Therapeutics 125
CHAPTER 8 HBV VACCINES: LATE-STAGE PIPELINE ANALYSIS 127
Summary 127
Overview for prophylactic HBV vaccines 127
Pipeline summary 127
Definition of current comparator therapy 128
Engerix-B 129
Key improvement opportunities 131
Heplisav 131
Vaccine overview 131
Clinical trial data 132
Patient potential 138
Marketing factors 138
Satisfaction of unmet needs 139
Datamonitor vaccine assessment summary 139
Other late-stage HBV vaccine candidates 140
Sci-B-Vac (SciGen) 140
Supervax (Dynavax) 141
Overview for therapeutic HBV vaccines 142
Pipeline overview 143
Hepatitis B Therapeutic Vaccine (Emergent BioSolutions) 144
Hi-8 Hepatitis B Vaccine (Oxford BioMedica) 144
CHAPTER 9 HBV THERAPEUTICS: LATE-STAGE PIPELINE ANALYSIS AND FORECAST 146
Summary 146
Overview for HBV therapeutics 146
Pipeline summary 146
Assessment of clinical and commercial attractiveness 150
Comparative forecasts 151
Definition of current comparator therapy 151
Tenofovir/emtricitabine 154
Drug overview 154
Clinical trial data 155
Trials investigating tenofovir as monotherapy in CHB patients 155
Trials investigating tenofovir in combination with emtricitabine in CHB patients 158
Trials investigating tenofovir with and without emtricitabine in HIV-HBV co-infected patients 160
Patient potential 162
Marketing factors 163
Satisfaction of unmet needs 163
Forecasts to 2016 164
Datamonitor drug assessment summary 166
Clevudine 167
Drug overview 167
Clinical trial data 168
The Korean Phase III trials - more data needed on long-term efficacy 172
Patient potential 176
Marketing factors 176
Satisfaction of unmet needs 177
Forecasts to 2016 177
Datamonitor drug assessment summary 179
Other HBV therapeutics in late-stage development 181
Valtorcitabine (Novartis/Idenix) 181
EHT899 (Enzo Biochem Inc) 182
Nitazoxanide (Romark Laboratories LC) 182
Elvucitabine (Achillion Pharmaceuticals) 183
Immunitin/HE2000 (Hollis-Eden Pharmaceuticals) 184
Late-stage development compounds recently discontinued 184
Pradefovir (Metabasis Therapeutics/Valeant/Schering-Plough) 184
CHAPTER 10 COMBINATION THERAPIES 186
Summary 186
Combination therapy would prove a valuable alternative in resistant patients and potentially increase the chance of eradicating the virus 186
Combinations between two antivirals 188
Lamivudine plus adefovir dipivoxil - no benefits in efficacy, but in decelerating resistance development 189
Combinations with telbivudine - potential benefits with tenofovir, adefovir or valtorcitabine? 192
Tenofovir plus emtricitabine - extending Truvada's success in HIV? 194
Others - focus on entecavir plus nucleotides 194
Combinations between one interferon and one antiviral 197
Combinations with peginterferon alfa-2a - building on the success in HCV treatment? 197
Combinations with interferon alfa-2b - no added value in efficacy shown for lamivudine and ribavirin 200
BIBLIOGRAPHY 204
Literature 204
APPENDIX A - MARKET FORECAST DATA 217
Seven major markets 217
EU5 218
US 219
Japan 220
France 221
Germany 222
Italy 223
Spain 224
UK 225
APPENDIX B 226
Methodology 226
Datamonitor forecast methodology 226
Epidemiology forecasts 226
Product forecasts 226
Definition of a standard unit 226
Datamonitor drug assessment summary 227
About Datamonitor 228
About Datamonitor Healthcare 228
Datamonitor Healthcare's therapy area capabilities 229
About the Infectious Diseases analysis team 230
Key therapy team members 231
Holger Rovini, Head of Respiratory and Infectious Diseases 231
Hedwig Kresse, Analyst, Infectious Diseases 231
Disclaimer 231
List of Tables
Table 1: Key parameters of Hepatitis B for the seven major markets, 2006-2016 6
Table 2: Forecast key products in Hepatitis B; 7MM, 2006-2016 ($m) 6
Table 3: HBV nomenclature - viral and host-derived serum markers 24
Table 4: HBV serology - diagnosis results 25
Table 5: HBV - prevalence, diagnosis and treatment rates across the 7MM, 2004 40
Table 6: Hep B vaccines - key products, 2007 59
Table 7: Currently marketed HBV drugs 66
Table 8: Factors influencing the choice of first-line therapy for HBV 67
Table 9: HBV treatment options - comparison of resistances, mode of administration, safety profile and duration of treatment 69
Table 10: HBV therapy with interferons - factors indicating the likelihood of response 72
Table 11: Intron A: product profile 74
Table 12: Events impacting sales forecast for Intron-A, 2006-2016 77
Table 13: Pegasys: product profile 78
Table 14: Events impacting sales forecast for Pegasys, 2006-2016 81
Table 15: Mechanism of currently marketed antivirals, 2007 83
Table 16: Zeffix: product profile 85
Table 17: Events impacting sales forecast for Zeffix; 2006-2016 88
Table 18: Hepsera: product profile 90
Table 19: Events impacting sales forecast for Hepsera; 2006-2016 93
Table 20: Baraclude: product profile 94
Table 21: Events impacting sales forecast for Baraclude 2006-2016 97
Table 22: Tyzeka: product profile 99
Table 23: Events impacting sales forecast for Tyzeka, 2006-2016 102
Table 24: Key players in the hepatitis B market, 2007 106
Table 25: Datamonitor's launch dates for HBV therapeutics in the 7MM, 2007-2016 120
Table 26: Patent expiry dates for HBV therapeutics in the 7MM, 2007-2016 121
Table 27: Number of key hepatitis B pipeline candidates by class and phase of development, September 2007 124
Table 28: HBV prophylactic vaccines pipeline - overview, September 2007 128
Table 29: Engerix-B - vaccine profile 129
Table 30: Heplisav - vaccine profile 131
Table 31: Heplisav - key Phase III clinical trials, 2007 133
Table 32: Heplisav - key Phase II clinical trials, 2007 134
Table 33: HBV therapeutic vaccines pipeline - overview, September 2007 143
Table 34: HBV therapy - clinical pipeline overview, 2007 148
Table 35: HBV therapy - preclinical pipeline overview, 2007 149
Table 36: Entecavir - comparative profile 153
Table 37: Tenofovir - product profile 154
Table 38: Tenofovir - clinical trials for monotherapy, 2007 156
Table 39: Tenofovir - trials for HBV therapy with tenofovir plus emtricitabine (Truvada) 159
Table 40: Tenofovir - Trials for HIV/HBV co-infection 161
Table 41: Impacting factors on the revenues of tenofovir, 2006-2016 165
Table 42: Clevudine - drug profile 168
Table 43: Clevudine - terminated clinical trials in Korea 169
Table 44: Clevudine - ongoing clinical trials 171
Table 45: Impacting factors on the revenues of clevudine, 2006-2016 179
Table 46: Recently discontinued HBV therapeutics, 2007 184
Table 47: Combination therapies - clinical trials for lamivudine + adefovir dipivoxil 190
Table 48: Combination therapies - clinical trials for combinations involving telbivudine 193
Table 49: Combination therapies - other clinical trials 196
Table 50: Combination therapies - clinical trials based on peginterferon alfa-2a 199
Table 51: Combination therapies - clinical trials based on interferon alfa-2b 201
Table 52: Seven major market Hepatitis B drug sales ($000s) forecasts, 2006-2016 217
Table 53: EU5 Hepatitis B drug sales ($000s) forecasts, 2006-2016 218
Table 54: US Hepatitis B drug sales ($000s) forecasts, 2006-2016 219