Commercial Insight: Select herpes viruses and human papilloma virus - Non-biologic interventions for oral and genital herpes, cytomegalovirus infection, herpes zoster and genital warts

Commercial Insight: Select herpes viruses and human papilloma virus - Non-biologic interventions for oral and genital herpes, cytomegalovirus infection, herpes zoster and genital warts

CHAPTER 1 EXECUTIVE SUMMARY 3
Strategic scoping and focus 3
Datamonitor insight into the disease market 3
Related reports 5
Upcoming related reports 5

CHAPTER 2 MARKET DEFINITION 7
Market definition for this report 7
Pathogens and disease indications 10
Herpes simplex viruses 11
Primitive herpes simplex virus (HSV) prophylaxis 14
Reducing the frequency of recurrence 17
Reducing the impact of recurrence 21
Varicella zoster virus 22
The vaccination paradox 24
Ambiguous early signs - a major barrier to necessary early treatment 26
Continued reliance on alleviating symptoms does not solve the problem of post-herpetic neuralgia 27
Vaccination - an advance, but by no means a complete solution 28
Preventing the damage - new antiviral trials emphasize prevention of post-herpetic neuralgia 30
Zoster complications as a non-infectious disease sector 30
Human papillomavirus 31
Barriers to vaccine uptake - universal adoption is not a given 34
Continued demand for non-vaccine interventions 36
Cytomegalovirus 36
Congenital cytomegalovirus 37
Acquired cytomegalovirus infection 39

CHAPTER 3 PATIENT ACQUISITION PROCESS 41
Introduction 41
Herpes simplex virus type 1 and 2 patient care pathways 45
Self-diagnosis and treatment of herpes 47
Initial presentation 48
Managing transmission risk 48
Varicella zoster virus patient care pathways 49
Pediatric illness - the curse of the industry dollar 50
A bitter pill for pediatric vaccines 51
General education - leave it to the [medical] professionals 51
Adult illness 52
Decision making and decision makers in advanced age 52
High presentation rates, but early enough? 53
Human papillomavirus patient care path 53
Cytomegalovirus patient care path 55

CHAPTER 4 MARKET OVERVIEW 58
Market Overview 58
Seven major markets versus rest of world 60
Seven major markets drive market value despite high volume growth in rest of market 61
Seven major market HSV/VZV sectors dominate the market, but interesting signs of growth elsewhere 64
Relative shelter from generic incursion in the seven major markets and further afield 66
Seven major markets 68
Key market events and characteristics 68
Current market assessment 71
US commands highest value sales but Japan is pushing volume sales 71
Herpes simplex virus and varicella zoster virus sectors dominate, and newer treatments drive value growth 74
Branded sales volumes take a small but important generic hit 77
Very high concentration around leading brands in each sector 79
Future market assessment 84
US to take the biggest hit as growth rates start to falter 86
Major, but sector-specific genericization is imminent 88
Generic domination threatens the likelihood of new blood and new solutions 90
Few survivors of the generic tidal wave 93
Opportunities and threats 98
Still no cures 99
Respite from the looming threat of vaccines? 102
The curse of aciclovir 104
Genital warts and beyond 113
The vaccine-antiviral combination approach 116
Reducing toxicity in patients least able to tolerate it 119
US 125
Key event summary 126
Current market assessment 129
The US HSV/VZV sector is the defining sector of the seven major markets 129
Strong generic growth bested by brands taking new and switch prescriptions? 132
Valtrex drives three-quarters of US growth 135
Future market assessment 139
Brand expansion of patient populations fuels future growth - in all sectors but human papillomavirus 140
From a heavily branded sector to a generic haven in less than 10 years 142
Valtrex patent expiry: side effects may include portfolio headaches 144
Japan 149
Key market events 150
Current market assessment 152
High growth market, even in traditionally miniscule sectors 152
Japan goes generic 156
Japan shows a preference for budget products 160
Future market assessment 164
CMV - the resilient sector 165
The big slowdown - brands first 166
Less about Valtrex, more about Valcyte 168
5EU 172
Key market events 172
Current market assessment 174
Higher emphasis on CMV and HPV 174
Not the cheapest brands, and higher generic costs, but much smaller margin between the two 178
More even distribution of revenues 181
Future market assessment 185
Cytomegalovirus sector growth offsets losses elsewhere 185
Brand versus generic 187
Key brands 189

CHAPTER 5 BRAND DYNAMICS 193
Herpes simplex virus and varicella zoster virus 193
Overview of competitive landscape 193
Key issues in brand preference 195
Genital herpes 197
Oral herpes 198
Varicella zoster 199
Herpes zoster 199
US formulary status for leading brands 199
Pipeline profile 201
Valtrex - the current gold standard 203
Drug profile 204
Product positioning 206
Brand forecast to 2017 209
Strategic recommendations 212
Cytomegalovirus 214
Valcyte's capture of the cytomegalovirus market 215
Limited options drive brand choice 218
Cause or effect: necessity drives US formulary status 219
Practical information has greater impact than brand positioning? 219
Maribavir - filling the gaps in transplant indications 220
Brand forecast to 2017 223
Strategic recommendations 226
Human papillomavirus 227
Overview of competitive landscape 227
Drivers of brand choice 229
US formulary status for leading brands 231
Pipeline profile 231
Brand forecasts to 2017 233
Strategic recommendations 235

BIBLIOGRAPHY 237
Journal papers 237
Websites 243
Articles 244
Books 245
Datamonitor reports 245
Other 246

APPENDIX A - MARKET ASSUMPTION 247
Background 5EU Sales data 247
New product launches 256
Patent expiries 256
Data definitions, limitations and assumptions 257
Standard units 257
Japanese market data 257
Derivation of sales forecasts and pricing trends 258
Other points of note 258
Distribution of specialist products and sales data collection methodologies. 258
Forecast methodology 259

APPENDIX B 260
Contributing experts 260
Report methodology 260
About Datamonitor 260
About Datamonitor Healthcare 260
About the Infectious Disease analysis team 261
Disclaimer 263

List of Tables
Table 1: Herpes, varicella, cytomegalovirus and human papillomavirus antivirals analyzed and forecast in this report, 2008 8
Table 2: Infectious agents and indications covered in this report 10
Table 3: Human herpes virus subfamilies and their constituent members 12
Table 4: Trends in herpes simplex virus type 1 and type 2 sero-prevalence in the US, 1988-1994 and 1999--2004 15
Table 5: Threshold for sustainable transmission and transmission probability per partnership for key sexually transmitted infections, 2008 21
Table 6: Herpes zoster incidence in the US and EU 25
Table 7: Zostavax efficacy in preventing herpes zoster and post-herpetic neuralgia (PHN) in patients developing herpes zoster post-vaccination 29
Table 8: Non-antiviral interventions for post-herpetic neuralgia 31
Table 9: Human papillomavirus: comparative analysis of Gardasil and Cervarix 33
Table 10: Herpes simplex virus (HSV), varicella zoster virus (VZV), human papillomavirus (HPV) and cytomegalovirus (CMV): key factors influencing patient flow through the healthcare system 44
Table 11: Key* antiviral market sales by value, seven major markets (7MM) versus rest of world (ROW), indexed (2003-07) and actual (2007) 62
Table 12: Key* antiviral market sales by volume, seven major markets (7MM) versus rest of world (ROW), indexed (2003-07) and actual (2007) 63
Table 13: Seven major market (7MM) and rest of world (ROW) antiviral sales by volume and sector, 2007 65
Table 14: Seven major market (7MM) and rest of world (ROW) antiviral sales by value and sector, 2007 66
Table 15: Seven major market (7MM) and rest of world (ROW) antiviral brand and generic value sales (2007) and key dynamics (volume and value growth rates, 2003-07) 68
Table 16: Indexed antiviral sector sales by value in the seven major markets by region, 2003-07 72
Table 17: Indexed antiviral sector sales by volume in the seven major markets by region, 2003-07 73
Table 18: Indexed antiviral value sales by sector in the seven major markets, 2003-07 75
Table 19: Indexed antiviral volume sales by sector in the seven major markets, 2003-07 76
Table 20: Indexed generic versus branded antiviral value sales in the seven major markets, 2003-07 78
Table 21: Indexed generic versus branded antiviral volume sales in the seven major markets, 2003-07 79
Table 22: Indexed value sales for key antiviral brands in the seven major markets, 2003-07 82
Table 23: Indexed volume sales for key antiviral brands in the seven major markets, 2003-07 83
Table 24: Seven major market performance of the herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets by region, 2007 and 2017 88
Table 25: Seven major market sector performance of the herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, 2007 and 2017 90
Table 26: Seven major market sector performance of herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, branded versus generic sales, 2007 and 2017 93
Table 27: Seven major market herpes simplex virus, varicella zoster virus, cytomegalovirus and human papillomavirus antiviral sales ($m) forecasts, 2007-2017 96
Table 28: Herpes simplex and varicella zoster, cytomegalovirus and human papillomavirus virus all-sector scenario assessment - finding a curative or suppressive therapy 99
Table 29: Herpes simplex and varicella zoster, cytomegalovirus and human papillomavirus virus all-sector scenario assessment - vaccines do not displace need for antiviral therapies 102
Table 30: Herpes simplex and varicella zoster virus scenario assessment - aciclovir sets the bar too high 104
Table 31: Herpes simplex and varicella zoster virus scenario assessment - lowering the price of generic valaciclovir to compete with branded oral aciclovir 106
Table 32: Varicella zoster virus scenario assessment - upfront investment to improve understanding of viral involvement in post-herpetic neuralgia 108
Table 33: Human papillomavirus scenario assessment - leveraging new genital warts treatments into much broader applications 113
Table 34: Human papillomavirus scenario assessment - using an HPV antiviral to increase the potential market for HPV vaccines 116
Table 35: Cytomegalovirus scenario assessment - providing a less toxic alternative for cytomegalovirus 119
Table 36: Cytomegalovirus scenario assessment - improvement in the management of acquired and induced immunosuppression 123
Table 37: US herpes simplex and varicella zoster virus sector timeline, 1977-2015 126
Table 38: US human papillomavirus sector timeline, 1991-2013 128
Table 39: US cytomegalovirus sector timeline, 1988-2015 128
Table 40: Indexed US antiviral value sales by sector in the US, 2003-07 131
Table 41: Indexed US antiviral volume sales by sector in the US, 2003-07 132
Table 42: Indexed US antivirals brand versus generic value sales, 2003-07 133
Table 43: Indexed US antivirals brand versus generic volume sales, 2003-07 135
Table 44: Indexed value sales, CAGR (2003-07) and actual sales (2007) for key antiviral brands 137
Table 45: Indexed US volume sales, CAGR (2003-07) and actual sales (2007) for key antiviral brands 139
Table 46: US sector performance of the herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, 2007 and 2017 142
Table 47: US performance of herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, branded versus generic sales, 2007 and 2017 144
Table 48: Indexed US value sales for key antiviral brands, 2007-2017 146
Table 49: US herpes simplex virus, varicella zoster virus, cytomegalovirus and human papillomavirus antiviral sales ($m) forecasts, 2007-2017 147
Table 50: Japanese herpes simplex and varicella zoster virus sector timeline, 1984-2015 150
Table 51: Japanese human papillomavirus sector timeline, 2004-2013 151
Table 52: Japanese cytomegalovirus sector timeline, 1988-2016 151
Table 53: Indexed Japanese antiviral value sales by sector, 2003-07 155
Table 54: Indexed Japanese antiviral volume sales by sector, 2003-07 156
Table 55: Indexed Japanese antiviral brand versus generic value sales, 2003-07 158
Table 56: Indexed Japanese antiviral brand versus generic volume sales, 2003-07 159
Table 57: Indexed Japanese value sales for key antiviral brands, 2003-07 162
Table 58: Indexed Japanesevolume sales for key antiviral brands, 2003-07 164
Table 59: Japanese sector performance of the herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, 2007 and 2017 166
Table 60: Japanese performance of herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, branded versus generic sales, 2007 and 2017 168
Table 61: Japanese herpes simplex virus, varicella zoster virus, cytomegalovirus and human papillomavirus antiviral sales ($m) forecasts, 2007-2017 170
Table 62: 5EU herpes simplex and varicella zoster virus sector timeline, 2007-2016 173
Table 63: 5EU human papillomavirus sector timeline, 2009 173
Table 64: 5EU cytomegalovirus sector timeline, 2007-2016 174
Table 65: Indexed 5EU antiviral value sales by sector, 2003-07 176
Table 66: Indexed antiviral volume sales by sector in the 5EU, 2003-07 178
Table 67: Indexed 5EU antiviral brand versus generic value sales, 2003-07 179
Table 68: Indexed 5EU antiviral brand versus generic volume sales, 2003-07 181
Table 69: Indexed 5EU value sales for key antiviral brands, 2003-07 183
Table 70: Indexed 5EU volume sales for key antiviral brands, 2003-07 185
Table 71: 5EU sector performance of the herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, 2007 and 2017 187
Table 72: 5EU performance of herpes simplex virus and varicella zoster virus, cytomegalovirus and human papilloma markets, branded versus generic sales, 2007 and 2017 189
Table 73: 5EU herpes simplex virus, varicella zoster virus, cytomegalovirus and human papillomavirus antiviral sales ($m) forecasts, 2007-2017 191
Table 74: Leading branded drug sales ($m) for herpes simplex and varicella zoster virus, 2007-17 195
Table 75: Relative dosing and unit cost for Zovirax, Famvir and Valtrex 196
Table 76: Current formulary status for leading brands in the herpes simplex and varicella zoster virus sector 200
Table 77: Pipeline products in clinical development for herpes simplex virus and varicella zoster virus, 2007 202
Table 78: Valtrex - key facts, 2008 204
Table 79: Seven major market sales forecast ($m) for Valtrex, 2007-17 211
Table 80: Impacting factors on valaciclovir revenues, 2007-2017 211
Table 81: Leading branded drug sales ($m) for cytomegalovirus, 2007-2017 218
Table 82: Current formulary status for leading brands in cytomegalovirus sector for selected US healthcare plans 219
Table 83: Pipeline products in clinical development for herpes simplex virus and varicella zoster virus, 2007 220
Table 84: Timeline for maribavir clinical development, 2006-2011 223