Abstract
Overview
Introduction
More people than ever are living with HIV and AIDS in North America and Western Europe. Over the next five years, a great variety of new HIV drugs are expected to reach the market - early stage therapies will be simplified by new products that will transform the market. For those with few treatment options left, new pipeline products will redefine late stage therapy.
Scope
- Discussion of the epidemiology dynamics of HIV in the seven major markets, as well as the changing unmet needs that result
- Assessment of late-phase clinical development compounds, competitors, and opinion leader comments on trial design
- Forecasted sales of drugs in the antiretroviral market for the next 10 years
- Examination of the emerging drug classes including Entry Inhibitors and Integrase Inhibitors
Report Highlights
The increased use of antiretroviral agents has been accompanied by a rise in resistance to these drugs. Resistance generally falls into two categories: natural and acquired. The factors surrounding the development of HIV resistance are interrelated and include poor drug compliance, pharmacological factors, and direct molecular drug resistance.
Atripla, approved in the US in July 2006, has been one of the greatest developments in HIV therapy. A combination of two class leaders, Truvada and Sustiva, the triple pill is the first to combine the components of HAART into a single pill formulation taken once daily. Datamonitor forecasts it to reach peak sales in excess of $2 billion.
Integrase inhibitors MK-0518 and GS-9137 look to be the most promising candidates in the EI and others pipeline. Of the two, MK-0518 is the most advanced and looks set to dominate the salvage market.
Reasons to Purchase
- Understand key drivers in the antiretroviral market and predict the future performance of key compounds
- Explore the changing unmet needs of patients and clinical endpoints used in current trial design
- Evaluate forecasts for the antiretroviral market to 2015, taking into account key launch dates, patent expiries and generic incursion
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- About the Infectious Diseases & Respiratory pharmaceutical analysis team
- CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- More people than ever living with HIV and AIDS in North America and Western and Central Europe
- Contributing experts
- Datamonitor insight into the HIV market
- In the main line HIV treatments, Truvada-containing regimes have taken over from Combivir as the new gold standard for the NRTI class and patient simplicity will be greatly improved with the launch of Atripla.
- Non-nucleoside analogs (NNRTIs) are dominated by Sustiva and physicians have few choices when drug resistance develops.
- Despite a large number of available products, two Protease Inhibitors (PIs) have over half the class market share. The role of PIs in salvage therapy is being re-defined by Prezista and Aptivus, yet a gold standard here has not yet emerged.
- Entry Inhibitors (EIs), integrase inhibitors and other new drug classes represent a major opportunity for new product development but are initially targeting the small salvage market
- Scope of the analysis
- CHAPTER 2 PATIENT POTENTIAL
- Definition of HIV
- Epidemiology of HIV
- Growing epidemics are underway in Eastern Europe, Central Asia and India
- More people than ever living with HIV and AIDS in North America and Western and Central Europe
- Increased HIV diagnosis is driven by immigration, a rise in risky
behavior, more convenient diagnostics and braoder testing guidelines
- Immigration from areas of high prevalence means the need for antiretroviral therapy in the seven major markets will continue to grow
- Improved HIV tests and changes in CDC HIV testing guidelines should increase the HIV diagnosis and treatment rates and might reduce HIV transmission
- The perception that HIV is a manageable condition and not a 'death sentence' has led to a rise in risky behavior, particularly among the younger age groups
- The increased number of women becoming infected is driven by heterosexual intercourse
- Concentration of HIV infections among Africa Americans and Hispanic Americans
- Increased occurrence of HIV drug resistance in treatment-na�Ee patients is affecting front line treatment strategies
- Treatment efficacy remains the primary unmet medical need
- Side effects and drug resistance are key unmet medical needs in
individual drug classes
- Drug resistance is a problem in most HIV drug classes - but for different reasons
- Despite good efficacy, PIs are plagued by drug interactions, resistance and side effects
- 'Pill burden' is no longer an unmet need across the ARV drug classes
- No one issue stands out with NRTIs; new drugs must be good 'all round'
- Entry Inhibitors have commanded a premium price; this has made physicians wary of this drug class
- CHAPTER 3 R&D APPROACH
- Overview of HIV drug classes
- Nucleoside analogs (NRTIs), the oldest HIV drug class, have a mature market dynamic and physicians may choose between many available products
- Non-nucleoside analogs (NNRTIs) are dominated by Sustiva and physicians have few choices when drug resistance develops
- Despite a large number of available products, two Protease Inhibitors (PIs) take over half the class market share
- Entry Inhibitors (EIs) and other new drug classes represent a major opportunity for new product development but are targeted to the small salvage market when first launched
- Clinical trial endpoints are shifting in response to the newer unmet
needs in HIV
- Early trial were based on 'hard' clinical endpoints, such as progression to AIDS or death
- 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
- Reduction in viral load
- CD4 Elevation
- Efficacy Equivalence
- With improved understanding of HIV and the advent of HAART therapy,
endpoints have changed significantly
- Activity against resistant virus - a must for most of the HIV pipeline
- Quality of life considerations
- Overview of HIV drug classes
- CHAPTER 4 HIV PIPELINE ANALYSIS
- Pipeline overview
- A collaboration between Gilead and BMS has produced Atripla, the first of its kind
- Tibotec J&Js highly anticipated pipeline products set to generate significant revenues for J&J
- GSK currently dominates HIV market but with only one pipeline product its market share will be drastically reduced by 2016
- CHAPTER 5 NRTI LATE-STAGE DRUG ANALYSIS & FORECASTS
- Fixed dose combinations dominate the NRTI market
- Truvada-containing regimes replace Combivir as the new gold standard
- Once daily Atripla eliminates the issue of pill burden and is forecast to become the first HIV blockbuster
- Pipeline products attempt to tackle drug resistance
- Multi-nucleoside resistance
- Development of new drugs has been slow
- Elvucitabine
- Clinical trial data
- Datamonitor analysis
- Racivir
- Clinical trial data
- Datamonitor analysis
- AVX-754
- Clinical trial data
- Datamonitor analysis
- MIV-210
- Clinical trial data
- Datamonitor analysis
- Amdoxovir
- Clinical trial data
- Datamonitor analysis
- Late-stage development compounds recently discontinued
- Reverset
- Fixed dose combinations dominate the NRTI market
- CHAPTER 6 NNRTI LATE-STAGE DRUG ANALYSIS AND FORECASTS
- The NNRTIs are recommended for first line therapy, but can only be used
for a limited time before class resistance develops.
- Sustiva maintains its grip on the market and its gold-standard status
- Class wide resistance is the primary unmet need for the NNRTIs and its prevalence is growing in treatment na�Ee patients
- Pipeline NNRTIs are addressing the greatest unmet need for this class
- TMC125
- Clinical trial data
- Datamonitor analysis
- TMC278
- Clinical trial data
- Datamonitor analysis
- BILR355
- Clinical trial data
- Datamonitor analysis
- Innovative Early-Stage Project
- Calanolide A
- Late-stage development compounds recently discontinued
- Capravirine
- GW-695634
- MIV-150
- The NNRTIs are recommended for first line therapy, but can only be used
for a limited time before class resistance develops.
- CHAPTER 7 PI LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview of current PI Market
- Boosting with ritonavir improves pharmacokinetics, increases efficacy and is now standard practice; Abbott's ownership of ritonavir gives it a competitive advantage in the PI market
- Kaletra the gold standard in the PI class is now available in once daily, temperature stable tablets without food restrictions
- The competitive pressure from Reyataz is strong
- Current developmental compounds tackle resistance but not side effects or drug-drug interactions
- Aptivus (tipranavir)
- Clinical trial data
- Datamonitor analysis
- Prezista (TMC114)
- Clinical trial data
- Datamonitor analysis
- Brecanavir
- Clinical trial data
- Datamonitor analysis
- Innovative early-stage projects
- PPL-100
- Overview of current PI Market
- CHAPTER 8 EI AND OTHER LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview of current EI Market
- There is no gold standard treatment in the EI drug class; Fuzeon sales are limited to the salvage market
- Roche and Trimeris aim for once weekly needle-free T-20 to increase patient tolerability
- Fuzeon boosts efficacy of other products
- The EI and others pipeline encompasses a wide range of products, with a
variety of targets and mechanisms of action being investigated
- CCR5 and CXCR4 receptors have become important antiretroviral targets as the two main co-receptors essential for HIV entry into uninfected cells
- CCR5 Inhibitors- poor results from most pipeline compounds have
tarnished the reputation of this class
- Vicriviroc
- Clinical trial data
- Datamonitor analysis
- Vicriviroc
- Maraviroc
- Clinical trial data
- Datamonitor analysis
- CXCR4 inhibitors
- AMD070
- Clinical trial data
- Datamonitor analysis
- AMD070
- Attachment inhibitors
- TNX-355
- Clinical trial data
- Datamonitor analysis
- TNX-355
- Integrase Inhibitors
- MK-0518
- Clinical trial data
- Datamonitor analysis
- GS-9137
- Clinical trial data
- Datamonitor analysis
- MK-0518
- Maturation Inhibitors
- Bevirimat (PA-457)
- Clinical trial data
- Datamonitor analysis
- Bevirimat (PA-457)
- Innovative Early-Stage Projects
- PRO-140
- TRI-999 and TRI-1144
- Overview of current EI Market
- APPENDIX A
- Methodology
- Datamonitor forecast methodology.
- Epidemiology forecasts
- Product forecasts
- Definition of a standard unit
- Estimation of launch dates
- Datamonitor forecast methodology.
- Datamonitor drug assessment summary
- Contributing experts
- Bibliography and Press Releases
- Frequently Used Websites
- Company websites
- Methodology
- APPENDIX B
- About Datamonitor
- About Datamonitor Healthcare
- Datamonitor Healthcare's therapy area capabilities
- About the Infectious disease analysis team
- Key therapy team members
- Mansi Shah, Analyst, Infectious Diseases
- Morris Paterson, Senior Analyst, Infectious Diseases
- Disclaimer
- List of Tables
- Table 1: Regional HIV and AIDS overview, 2005
- Table 2: DHHS and BHIVA HIV treatment guidelines
- Table 3: DHHS and BHIVA HIV recommended treatment combinations
- Table 4: Overview of the HIV pipeline by company
- Table 5: Overview of number of marketed drugs and developmental drugs for key HIV companies
- Table 6: Overview of Currently Marketed NRTIs
- Table 7: Overview of NRTI drug pipeline
- Table 8: Key clinical trials of Elvucitabine
- Table 9: Overview of Phase II trial of Elvucitabine
- Table 10: Key clinical trials of AVX-754
- Table 11: Overview of current Phase IIb trial of of AVX-754
- Table 12: Key clinical trials of MIV-210
- Table 13: Key clinical trials of Amdoxovir
- Table 14: Overview of current Phase II trial of Amdoxovir
- Table 15: Overview of currently marketed NNRTIs
- Table 16: Overview of NNRTI drug pipeline
- Table 17: Key clinical trials of TMC125
- Table 18: Key clinical trials of TMC278
- Table 19: Overview of current Phase IIb trial of TMC278
- Table 20: Key clinical trials of BILR355
- Table 21: Overview of currently marketed PIs
- Table 22: Overview of PI drug pipeline and recently launched PIs
- Table 23: RESIST 1 & 2 trial summary
- Table 24: Key ongoing clinical trials for Prezista
- Table 25: Previous trials of Prezista
- Table 26: Key clinical trials of Brecanavir
- Table 27: Key clinical trials of Maraviroc
- Table 28: Key clinical trials of AMD070
- Table 29: Overview of the XACT trial
- Table 30: Key clinical trials of TNX-355
- Table 31: Overview of Phase II trial of TNX-355
- Table 32: Results from MK-0518 head-to-head trial with Sustiva
- Table 33: Key clinical trials of MK-0518
- Table 34: Overview of Phase II trial of MK-0518
- Table 35: Overview of Phase II trial of MK-0518
- Table 36: Key clinical trials of GS-9137
- Table 37: Overview of the Phase I/II study
- Table 38: Key clinical trials of PA-457
- Table 39: Overview of Phase IIa study of Bevirimat
- Table 40: Average development timeline of HIV NMEs
- Table 41: Estimated launch dates for the US and EU
- List of Figures
- Figure 1: Global HIV epidemic, 1990-2005
- Figure 2: HIV prevalence in the 7 major markets
- Figure 3: Annual HIV incidence, US, Germany and UK, 1995-2003
- Figure 4: HIV-infected individuals accessing treatment in the UK
- Figure 5: HIV incidence by transmission group in Western Europe
- Figure 6: HIV acquired through heterosexual contact in the UK
- Figure 7: Increased ratio of women infected in the 7 major markets
- Figure 8: Drug Resistance in Newly Diagnosed HIV +ve U.S. Individuals
- Figure 9: Drug Resistance in Newly Diagnosed HIV +ve UK Individuals
- Figure 10: A comparison of clinical trials evaluating 3 drug combinations
- Figure 11: Drivers of switching from first- to second-line ARV therapy
- Figure 12: Unmet medical needs in individual HIV drug classes, 2006
- Figure 13: Underlying causes of HIV drug resistance
- Figure 14: Improving Outcomes With Evolving Antiretroviral Regimens
- Figure 15: HIV virus lifecycle
- Figure 16: US quarterly sales of HIV drug classes, 2002-2005
- Figure 17: Market share within each ARV drug class, major markets 2005
- Figure 18: Overview of HIV drug development pipeline, 2006
- Figure 19: HIV market share 2005 and 2016
- Figure 20: 2016 antiretroviral sales by company
- Figure 21: Quarterly sales of currently marketed NRTIs
- Figure 22: Atripla sales forecast 2006-2016
- Figure 23: Mutations in the reverse transcriptase gene associated with resistance to NRTIs
- Figure 24: Prevalence of major drug resistance mutations (IAS-USA definitions) in patients failing HAART
- Figure 25: Levels of unmet needs in the NRTI class
- Figure 26: Elvucitabine sales forecast 2006-2016
- Figure 27: Racivir sales forecast 2006-2016
- Figure 28: AVX-754 sales forecast 2006-2016
- Figure 29: MIV-210 sales forecast 2006-2016
- Figure 30: Amdoxovir sales forecast 2006-2016
- Figure 31: Mutations in the reverse transcriptase gene associated with resistance to NNRTIs
- Figure 32: Level of unmet needs in the NNRTI class
- Figure 33: Activity of NNRTIs against resistance causing mutations
- Figure 34: SWOT analysis for TMC125
- Figure 35: TMC125 sales forecast 2006-2016
- Figure 36: SWOT analysis for TMC278
- Figure 37: TMC278 sales forecast 2006-2016
- Figure 38: SWOT analysis for BILR355
- Figure 39: BILR355 sales forecast 2006-2016
- Figure 40: Unmet needs in the PI class
- Figure 41: Mutations in the protease gene associated with resistance to PIs
- Figure 42: SWOT Analysis for Aptivus
- Figure 43: Aptivus sales forecast 2006-2016
- Figure 44: SWOT Analysis for Prezista
- Figure 45: Prezista sales forecast 2006-2016
- Figure 46: SWOT analysis for Brecanavir
- Figure 47: Brecanavir sales forecast 2006-2016
- Figure 48: HIV host cell entry mechanism
- Figure 49: Molecular structure of Fuzeon
- Figure 50: Unmet needs across the EIs and others class
- Figure 51: HIV infection of target cells takes place via chemokine receptors
- Figure 52: Prevalence of CCR5, CXCR4 and dual tropic strains
- Figure 53: SWOT analysis for vicriviroc
- Figure 54: Vicriviroc sales forecast 2006-2016
- Figure 55: SWOT analysis for Maraviroc
- Figure 56: Maraviroc sales forecast 2006-2016
- Figure 57: SWOT analysis for AMD070
- Figure 58: AMD070 sales forecast 2006-2016
- Figure 59: SWOT analysis for TNX355
- Figure 60: TNX355 sales forecast 2006-2016
- Figure 61: SWOT analysis for MK-0518
- Figure 62: MK-0518 sales forecast 2006-2016
- Figure 63: SWOT analysis for GS-9137
- Figure 64: GS-9137 sales forecast 2006-2016
- Figure 65: SWOT analysis for Bevirimat
- Figure 66: Bevirimat (PA-457) sales forecast 2006-2016
- About Datamonitor
