HIV：新興のヌクレオシド系逆転写酵素阻害薬（NRTI）は重大なアンメットニーズに対応するか

Abstract

Overview

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

• In-depth analysis of Phase II and III clinical development compounds and comprehensive overview of Phase I drugs
• Overview of the key companies involved in the HIV pipeline
• The epidemiology dynamics of HIV in the six major markets are discussed along with unmet needs that have evolved from the prolonged use of HAART
• Sales forecasts over the next 10 years for the each of the late-stage drugs

Report Highlights

Class drug resistance represents a major problem for the NNRTIs. The two late stage compounds, developed by Tibotec/J&J, address this issue. etravirine is the more advanced of the two, but rilpivirine convenient dosing schedule makes it the commercially more promising candidate.

New NRTIs in development have not generated much excitement in the HIV community since most of these compounds, including Avexa' s apricitabine, Achillion' s elvucitabine and Pharmasset' s Racivir. have only made slow progress over the last few years.

Historically, emerging drug resistance may have signaled overall treatment failure and hastened the onset of AIDS. While newer classes of drugs will enable patients with complex drug resistance to continue with successful antiretroviral therapy, exactly how they will be incorporated into traditional HAART regimens remains unclear at this stage.

Reasons to Purchase

• Understand the constantly evolving market dynamics of antiretroviral drugs
• Understand the changing unmet needs of patients and the extent to which pipeline drugs are addressing these issues
• Evaluate the forecast of key pipeline antiretroviral drugs to 2016, taking into account key launch dates, adressing of unmet needs and other factors

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Infectious Disease and Respiratory pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Datamonitor insight into the HIV market
  • Key metrics
  • Datamonitor Pipeline Assessment Summary
  • Related reports
• CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS
  • HIV pipeline overview
    • Growth in the HIV market will be driven by launch of new compounds and classes from 2007 onwards
  • Key companies involved in the HIV pipeline
    • GSK set to lose significant market share
    • Gilead' s fixed dose combinations dominating initial therapy
    • Merck' s promising pipeline will strengthen its presence in HIV
    • Tibotec positioning compounds across all lines of therapy
  • Key R&D company strategies
    • Major players in HIV are also developing their drugs for HBV as a secondary indication
• CHAPTER 3 HIV - MARKET POTENTIAL
  • Definition of disease HIV
  • Segmentation of HIV
    • Treatment-naïve patients
    • Treatment-experienced patients
  • Epidemiology of HIV
    • HIV prevalence in US and Western Europe increasing
    • MSM remains the predominant transmission group in the US
    • Immigration from areas of high prevalence driving the increase in number of HIV-infected patients in Western Europe
    • Prolonged life expectancy from HAART
    • Awareness campaigns increasing diagnosis rates in the US but not enough emphasis on testing in Western Europe
  • Unmet needs in HIV
    • Efficacy is generally not an issue for most classes
    • Resistance remains a key unmet need for the NRTIs and NNRTIs
    • Side effects are particularly problematic for PIs
    • Issue of pill burden eliminated by availability of simplified treatments
    • PIs are more commonly associated with drug-drug interactions
    • Cost is currently not an issue but likely to be problem in the future
• CHAPTER 4 R&D APPROACH
  • Antiretroviral drug classes
    • NRTIs are the oldest class of drugs and form the backbone of HAART regimens
    • NNRTIs are generally used in first-line but are prone to resistance
    • Despite the availability of several PIs, two members dominate this class
    • Selzentry and Isentress are latest additions to the entry inhibitors and others class
      • Entry inhibitors
      • Integrase inhibitors
    • First cross class combination - Atripla
  • Clinical trials in HIV
    • Clinical trial endpoints
      • Early trials 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
• CHAPTER 5 NUCLEOSIDE REVERSE TRANSCRIPTASE INHBITORS LATE-STAGE DRUG ANALYSIS & FORECASTS
  • Overview for NRTIs
    • Pipeline summary
    • Comparative forecasts
    • Definition of current comparator therapy
      • NRTI gold standard - Truvada
  • Apricitabine
    • Drug overview
    • Clinical trial data
    • Satisfaction of unmet needs
      • Resistance
      • Toxicity
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
    • Datamonitor drug assessment summary
  • Elvucitabine
    • Drug overview
    • Clinical trial data
    • Satisfaction of unmet needs
      • Resistance
      • Toxicity
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
    • Datamonitor drug assessment study
  • Racivir
    • Drug overview
    • Clinical trial data
    • Satisfaction of unmet needs
      • Resistance
      • Toxicity
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
    • Datamonitor drug assessment study
  • Other drugs in the NRTI class
    • MIV-210
    • Amdoxovir
• CHAPTER 6 NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Overview for the NNRTI class
    • Pipeline summary
    • Comparative forecasts
    • Definition of current comparator therapy
      • NNRTI ' gold-standard' : Sustiva
  • Etravirine
    • Drug overview
    • Clinical trial data
    • Satisfaction of unmet needs
      • Resistance
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
    • Datamonitor drug assessment study
  • Rilpivirine
    • Drug overview
    • Clinical trial data
    • Satisfaction of unmet needs
      • Resistance
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
    • Datamonitor drug assessment study
  • Other drugs in development from the NNRTI class
    • UK 453,061
    • RDEA806
    • IDX-899
• CHAPTER 7 PROTEASE INHIBITORS LATE STAGE DRUG ANALYSIS AND FORECASTS
  • Overview for the PI class
    • Pipeline summary
    • Definition of current comparator therapy
      • PI gold-standard Kaletra
      • Competitive pressure from Reyataz and Prezista
  • PIs in early stage development
    • MK-8122
    • GS-8374
    • SPI-256
  • Late-stage development compounds recently discontinued
    • Brecanavir
• CHAPTER 8 EIS AND OTHERS LATE STAGE DRUG ANALYSIS AND FORECASTS
  • Overview for the EI & others class
    • Pipeline summary
    • Comparative forecasts
    • Definition of current comparator therapy
      • Fuzeon
      • Selzentry/Celsentri
      • Drug assessment study for entry inhibitors
      • Isentress
  • Compounds in late-stage development
    • Elvitegravir
      • Drug overview
      • Clinical trial data
      • Patient potential
      • Marketing factors
      • Forecasts to 2016
  • Vicriviroc
    • Drug overview
    • Clinical trial data
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
    • Drug assessment study
  • Bevirimat
    • Drug overview
    • Clinical trial data
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
  • Other drugs in the EI and others class
    • PRO-140
    • Ibalizumab (TNX-355)
    • INCB9471
    • MK-2048
    • Vivecon (MPC-9055)
• APPENDIX A
  • Bibliography
    • Journal articles and conference abstracts
    • Websites
  • Methodology
    • Datamonitor forecast methodology
      • Epidemiology forecasts
      • Product forecasts
      • Definition of a standard unit (only use if ForeSight model used to forecast)
  • Contributing experts
• APPENDIX B
  • About Datamonitor
    • About Datamonitor Healthcare
  • Datamonitor Healthcare' s therapy area capabilities
    • About the Disease analysis team
    • Key therapy team members
      • Holger Rovini, Lead Analyst, Infectious Disease and Respiratory
    • Disclaimer
  • List of Tables
    • Table 1: Key parameters of HIV for the sixmajor markets
    • Table 2: HIV pipeline overview, 2007
    • Table 3: Overview of GSK' s HIV portfolio, 2007
    • Table 4: Overview of Gilead' s HIV portfolio, 2007
    • Table 5: Overview of the NRTIs, 2007
    • Table 6: Overview of the NNRTIs, 2007
    • Table 7: Overview of currently marketed PIs, 2007
    • Table 8: Key NRTI products in late-stage R&D pipeline for HIV, 2007
    • Table 9: Sales forecasts for pipeline NRTIs across the six major markets, 2006 -2015
    • Table 10: Gilead' s Truvada
    • Table 11: Key NNRTI products in late-stage R&D pipeline for HIV, 2007
    • Table 12: Sales forecasts for pipeline NNRTIs across the six major markets, 2007-2015
    • Table 13: BMS' s Sustiva
    • Table 14: Key PI products in early-stage R&D pipeline for HIV, 2007
    • Table 15: Abbott' s Kaletra
    • Table 16: Key EI and others products in late-stage R&D pipeline for HIV, 2007
    • Table 17: Datamonitor drug assessment parameters
  • List of Figures
    • Figure 1: Datamonitor drug assessment summary of pipeline drugs in late stage development for HIV, 2007
    • Figure 2: Number of compounds in late-stage development for HIV by class, 2007
    • Figure 3: Antiretroviral sales forecasts, six major markets, 2006-2016
    • Figure 4: HIV market share by company, 2003-06
    • Figure 5: Sales forecasts for Gilead products, six major markets, 2006-2016
    • Figure 6: Gilead HIV market share, 2006 and 2016
    • Figure 7: Sales forecasts for Prezista, etravirine and rilpivirine, six major markets, 2006-2016
    • Figure 8: Adults and children estimated to be living with HIV, 2007
    • Figure 9: Estimated number of people living with HIV globally, 1990-2007
    • Figure 10: Estimated number of people newly infected with HIV globally, 1990-2007
    • Figure 11: HIV diagnoses by exposure category, United Kingdom: 1981-2005
    • Figure 12: Number of newly diagnosed cases of HIV infection by transmission group and year of report in Western Europe (13 countries), 1999-2006
    • Figure 13: UK HIV diagnoses by the two main routes of transmission, 1997 -2004
    • Figure 14: HIV infections in the UK by the region they were acquired from, 2006
    • Figure 15: HIV lifecycle
    • Figure 16: Unmet needs for HIV drugs by class
    • Figure 17: Overview of sales of HIV treatments by drug class, 2002-06
    • Figure 18: HIV mechanism of entry into host cell
    • Figure 19: Datamonitor drug assessment summary of pipeline NRTIs
    • Figure 20: Sales forecasts for pipeline NRTIs across the six major markets, 2006-2016
    • Figure 21: Sales of Truvada. Epzicom and Combivir 2002-2006
    • Figure 22: Sales forecasts for apricitabine across the six major markets to 2016
    • Figure 23: Datamonitor' s competitive positioning analysis of apricitabine, 2007
    • Figure 24: Sales forecasts for elvucitabine across the six major markets to 2016
    • Figure 25: Datamonitor' s competitive positioning analysis of elvucitabine, 2007
    • Figure 26: Sales forecasts for racivir across the six major markets to 2016
    • Figure 27: Datamonitor' s competitive positioning analysis of racivir, 2007
    • Figure 28: Datamonitor drug assessment summary of pipeline NNRTIs
    • Figure 29: Sales forecasts for pipeline NNRTIs across the six major markets, 2006-2016
    • Figure 30: Sales of Sustiva Viramune and Rescriptor 2002-2006
    • Figure 31: DUET studies
    • Figure 32: Sales forecasts for etravirine across the six major markets to 2016
    • Figure 33: Datamonitor' s competitive positioning analysis of etravirine, 2007
    • Figure 34: Phase II program for rilpivirine
    • Figure 35: Sales forecasts for rilpivirine across the six major markets to 2016
    • Figure 36: Datamonitor' s competitive positioning analysis of rilpivirine, 2007
    • Figure 37: Sales of PIs 2002-2006
    • Figure 38: Sales forecasts for developmental and recently introduced EIs and others drugs, 6MM, 2006-2016
    • Figure 39: Overview of sales of Fuzeon in the US and Canada, 2003-06
    • Figure 40: MOTIVATE trials
    • Figure 41: MOTIVATE trial results
    • Figure 42: MERIT study
    • Figure 43: Sales forecasts for Selzentry across the six major markets to 2016
    • Figure 44: Datamonitor drug assessment summary of pipeline entry inhibitors
    • Figure 45: BENCHMARK trials
    • Figure 46: TRIO study
    • Figure 47: Sales forecasts for Isentress across the six major markets to 2016
    • Figure 48: Sales forecasts for elvitegravir across the six major markets to 2016
    • Figure 49: Sales forecasts for vicriviroc across the six major markets to 2016
    • Figure 50: Datamonitor' s competitive positioning analysis of rilpivirine, 2007
    • Figure 51: Sales forecasts for bevirimat across the six major markets to 2016
    • Figure 52: Datamonitor drug assessment summary of pipeline molecular targeted therapies in development for hematological malignancies, 2007