Introduction

Treatment of HIV has come a long way since the discovery of the virus. Although no real cure has been found yet, the last few decades have seen the introduction of many classes of drugs that suppress the replication of the virus. As therapeutics have improved dramatically in terms of efficacy, safety and convenience, the bar for new drugs has been raised considerably.

Scope

Table of Contents
ABOUT DATAMONITOR HEALTHCARE 2
About the Infectious Disease and Respiratory pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the HIV market 4
Key metrics 7
Datamonitor Pipeline Assessment Summary 8
Related reports 9
CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS 11
HIV pipeline overview 11
Growth in the HIV market will be driven by launch of new compounds and classes from 2007 onwards 13
Key companies involved in the HIV pipeline 16
GSK set to lose significant market share 16
Gilead's fixed dose combinations dominating initial therapy 19
Merck's promising pipeline will strengthen its presence in HIV 22
Tibotec positioning compounds across all lines of therapy 23
Key R&D company strategies 24
Major players in HIV are also developing their drugs for HBV as a secondary indication 24
CHAPTER 3 HIV - MARKET POTENTIAL 27
Definition of disease HIV 27
Segmentation of HIV 27
Treatment-naïve patients 27
Treatment-experienced patients 28
Epidemiology of HIV 28
HIV prevalence in US and Western Europe increasing 30
MSM remains the predominant transmission group in the US 31
Immigration from areas of high prevalence driving the increase in number of HIV-infected patients in Western Europe 34
Prolonged life expectancy from HAART 37
Awareness campaigns increasing diagnosis rates in the US but not enough emphasis on testing in Western Europe 37
Unmet needs in HIV 38
Efficacy is generally not an issue for most classes 40
Resistance remains a key unmet need for the NRTIs and NNRTIs 42
Side effects are particularly problematic for PIs 43
Issue of pill burden eliminated by availability of simplified treatments 44
PIs are more commonly associated with drug-drug interactions 45
Cost is currently not an issue but likely to be problem in the future 45
CHAPTER 4 R&D APPROACH 47
Antiretroviral drug classes 47
NRTIs are the oldest class of drugs and form the backbone of HAART regimens 48
NNRTIs are generally used in first-line but are prone to resistance 50
Despite the availability of several PIs, two members dominate this class 52
Selzentry and Isentress are latest additions to the entry inhibitors and others class 54
Entry inhibitors 54
Integrase inhibitors 56
First cross class combination - Atripla 56
Clinical trials in HIV 57
Clinical trial endpoints 58
Early trials were based on 'hard' clinical endpoints, such as progression to AIDS or death 58
The availability of HIV viral load diagnostics enabled trials to measure the direct effect on the virus, use 'soft' clinical endpoints and reduced the length of trials 59
Reduction in viral load 60
CD4 elevation 60
Efficacy equivalence 61
With improved understanding of HIV and the advent of HAART therapy, endpoints have changed significantly 61
Activity against resistant virus - a must for most of the HIV pipeline 61
Quality of life considerations 62
CHAPTER 5 NUCLEOSIDE REVERSE TRANSCRIPTASE INHBITORS LATE-STAGE DRUG ANALYSIS & FORECASTS 64
Overview for NRTIs 64
Pipeline summary 64
Comparative forecasts 66
Definition of current comparator therapy 68
NRTI gold standard - Truvada 68
Apricitabine 73
Drug overview 73
Clinical trial data 73
Satisfaction of unmet needs 74
Resistance 74
Toxicity 75
Patient potential 75
Marketing factors 75
Forecasts to 2016 76
Datamonitor drug assessment summary 77
Elvucitabine 78
Drug overview 78
Clinical trial data 79
Satisfaction of unmet needs 80
Resistance 80
Toxicity 81
Patient potential 81
Marketing factors 82
Forecasts to 2016 82
Datamonitor drug assessment study 83
Racivir 84
Drug overview 84
Clinical trial data 84
Satisfaction of unmet needs 85
Resistance 85
Toxicity 86
Patient potential 86
Marketing factors 86
Forecasts to 2016 87
Datamonitor drug assessment study 88
Other drugs in the NRTI class 89
MIV-210 89
Amdoxovir 89
CHAPTER 6 NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS LATE-STAGE DRUG ANALYSIS AND FORECASTS 91
Overview for the NNRTI class 91
Pipeline summary 91
Comparative forecasts 93
Definition of current comparator therapy 95
NNRTI 'gold-standard': Sustiva 95
Etravirine 99
Drug overview 99
Clinical trial data 99
Satisfaction of unmet needs 101
Resistance 101
Patient potential 102
Marketing factors 103
Forecasts to 2016 103
Datamonitor drug assessment study 104
Rilpivirine 105
Drug overview 105
Clinical trial data 106
Satisfaction of unmet needs 108
Resistance 108
Patient potential 108
Marketing factors 109
Forecasts to 2016 109
Datamonitor drug assessment study 110
Other drugs in development from the NNRTI class 110
UK 453,061 111
RDEA806 112
IDX-899 113
CHAPTER 7 PROTEASE INHIBITORS LATE STAGE DRUG ANALYSIS AND FORECASTS 115
Overview for the PI class 115
Pipeline summary 115
Definition of current comparator therapy 116
PI gold-standard Kaletra 116
Competitive pressure from Reyataz and Prezista 118
PIs in early stage development 121
MK-8122 121
GS-8374 123
SPI-256 123
Late-stage development compounds recently discontinued 124
Brecanavir 124
CHAPTER 8 EIS AND OTHERS LATE STAGE DRUG ANALYSIS AND FORECASTS 125
Overview for the EI & others class 125
Pipeline summary 125
Comparative forecasts 125
Definition of current comparator therapy 126
Fuzeon 126
Selzentry/Celsentri 127
Drug assessment study for entry inhibitors 132
Isentress 133
Compounds in late-stage development 137
Elvitegravir 138
Drug overview 138
Clinical trial data 138
Patient potential 139
Marketing factors 140
Forecasts to 2016 141
Vicriviroc 142
Drug overview 142
Clinical trial data 142
Patient potential 144
Marketing factors 144
Forecasts to 2016 145
Drug assessment study 145
Bevirimat 146
Drug overview 146
Clinical trial data 147
Patient potential 149
Marketing factors 150
Forecasts to 2016 150
Other drugs in the EI and others class 151
PRO-140 151
Ibalizumab (TNX-355) 152
INCB9471 153
MK-2048 154
Vivecon (MPC-9055) 154
APPENDIX A 156
Bibliography 156
Journal articles and conference abstracts 156
Websites 165
Methodology 167
Datamonitor forecast methodology 167
Epidemiology forecasts 167
Product forecasts 167
Definition of a standard unit (only use if ForeSight model used to forecast) 167
Contributing experts 170
APPENDIX B 172
About Datamonitor 172
About Datamonitor Healthcare 172
Datamonitor Healthcare's therapy area capabilities 173
About the Disease analysis team 174
Key therapy team members 175
Holger Rovini, Lead Analyst, Infectious Disease and Respiratory 175
Disclaimer 176
List of Tables
Table 1: Key parameters of HIV for the sixmajor markets 7
Table 2: HIV pipeline overview, 2007 12
Table 3: Overview of GSK's HIV portfolio, 2007 17
Table 4: Overview of Gilead's HIV portfolio, 2007 20
Table 5: Overview of the NRTIs, 2007 50
Table 6: Overview of the NNRTIs, 2007 51
Table 7: Overview of currently marketed PIs, 2007 53
Table 8: Key NRTI products in late-stage R&D pipeline for HIV, 2007 64
Table 9: Sales forecasts for pipeline NRTIs across the six major markets, 2006 -2015 67
Table 10: Gilead's Truvada 68
Table 11: Key NNRTI products in late-stage R&D pipeline for HIV, 2007 92
Table 12: Sales forecasts for pipeline NNRTIs across the six major markets, 2007-2015 94
Table 13: BMS's Sustiva 96
Table 14: Key PI products in early-stage R&D pipeline for HIV, 2007 116
Table 15: Abbott's Kaletra 117
Table 16: Key EI and others products in late-stage R&D pipeline for HIV, 2007 125
Table 17: Datamonitor drug assessment parameters 169
List of Figures
Figure 1: Datamonitor drug assessment summary of pipeline drugs in late stage development for HIV, 2007 8
Figure 2: Number of compounds in late-stage development for HIV by class, 2007 13
Figure 3: Antiretroviral sales forecasts, six major markets, 2006-2016 14
Figure 4: HIV market share by company, 2003-06 18
Figure 5: Sales forecasts for Gilead products, six major markets, 2006-2016 21
Figure 6: Gilead HIV market share, 2006 and 2016 22
Figure 7: Sales forecasts for Prezista, etravirine and rilpivirine, six major markets, 2006-2016 24
Figure 8: Adults and children estimated to be living with HIV, 2007 29
Figure 9: Estimated number of people living with HIV globally, 1990-2007 29
Figure 10: Estimated number of people newly infected with HIV globally, 1990-2007 30
Figure 11: HIV diagnoses by exposure category, United Kingdom: 1981-2005 32
Figure 12: Number of newly diagnosed cases of HIV infection by transmission group and year of report in Western Europe (13 countries), 1999-2006 33
Figure 13: UK HIV diagnoses by the two main routes of transmission, 1997 -2004 35
Figure 14: HIV infections in the UK by the region they were acquired from, 2006 36
Figure 15: HIV lifecycle 39
Figure 16: Unmet needs for HIV drugs by class 40
Figure 17: Overview of sales of HIV treatments by drug class, 2002-06 47
Figure 18: HIV mechanism of entry into host cell 55
Figure 19: Datamonitor drug assessment summary of pipeline NRTIs 66
Figure 20: Sales forecasts for pipeline NRTIs across the six major markets, 2006-2016 67
Figure 21: Sales of Truvada. Epzicom and Combivir 2002-2006 72
Figure 22: Sales forecasts for apricitabine across the six major markets to 2016 77
Figure 23: Datamonitor's competitive positioning analysis of apricitabine, 2007 78
Figure 24: Sales forecasts for elvucitabine across the six major markets to 2016 82
Figure 25: Datamonitor's competitive positioning analysis of elvucitabine, 2007 83
Figure 26: Sales forecasts for racivir across the six major markets to 2016 87
Figure 27: Datamonitor's competitive positioning analysis of racivir, 2007 88
Figure 28: Datamonitor drug assessment summary of pipeline NNRTIs 93
Figure 29: Sales forecasts for pipeline NNRTIs across the six major markets, 2006-2016 94
Figure 30: Sales of Sustiva Viramune and Rescriptor 2002-2006 97
Figure 31: DUET studies 100
Figure 32: Sales forecasts for etravirine across the six major markets to 2016 104
Figure 33: Datamonitor's competitive positioning analysis of etravirine, 2007 105
Figure 34: Phase II program for rilpivirine 107
Figure 35: Sales forecasts for rilpivirine across the six major markets to 2016 109
Figure 36: Datamonitor's competitive positioning analysis of rilpivirine, 2007 110
Figure 37: Sales of PIs 2002-2006 118
Figure 38: Sales forecasts for developmental and recently introduced EIs and others drugs, 6MM, 2006-2016 126
Figure 39: Overview of sales of Fuzeon in the US and Canada, 2003-06 127
Figure 40: MOTIVATE trials 128
Figure 41: MOTIVATE trial results 129
Figure 42: MERIT study 130
Figure 43: Sales forecasts for Selzentry across the six major markets to 2016 132
Figure 44: Datamonitor drug assessment summary of pipeline entry inhibitors 133
Figure 45: BENCHMARK trials 134
Figure 46: TRIO study 136
Figure 47: Sales forecasts for Isentress across the six major markets to 2016 137
Figure 48: Sales forecasts for elvitegravir across the six major markets to 2016 141
Figure 49: Sales forecasts for vicriviroc across the six major markets to 2016 145
Figure 50: Datamonitor's competitive positioning analysis of rilpivirine, 2007 146
Figure 51: Sales forecasts for bevirimat across the six major markets to 2016 151
Figure 52: Datamonitor drug assessment summary of pipeline molecular targeted therapies in development for hematological malignancies, 2007 170