Pipeline Insight: HIV - The Age of Convenience

Table of Contents

OVERVIEW

• Catalyst
• Summary

EXECUTIVE SUMMARY

• Strategic scoping and focus
• Datamonitor insight into the disease market
• Related reports

1. PIPELINE OVERVIEW AND DYNAMICS

• Key findings
• Pipeline overview
  • Comparative forecasts - cross-class fixed-dose combinations to dominate
  • Datamonitor Pipeline Assessment Summary

• Key companies involved in the HIV market
  • Gilead set to remain the HIV market leader
  • Key companies involved in the HIV pipeline

• Key R&D company strategies - collaborations and cross-class combinations
  • GlaxoSmithKline and Pfizer HIV merger
  • Gilead and Tibotec/Johnson & Johnson
  • Merck and Schering-Plough

2. HIV - MARKET POTENTIAL

• Key findings
• Definition
• Patient segmentation
  • Treatment-naive patients
  • Treatment-experienced patients

• Epidemiology
  • Seven major markets
  • Rest of the world

• Current treatment options
  • Nucleoside reverse transcriptase inhibitors
  • Non-nucleoside reverse transcriptase inhibitors
  • Protease inhibitors
  • Entry inhibitors
  • Integrase inhibitors
  • Cross-class combinations

• Current gold standard and comparator therapies
  • Atripla is widely accepted as the gold standard of HIV therapy
  • Choice of comparator differs for individual drug classes and treatment populations

• Current market overview
  • Atripla will surpass Truvada in 2009
  • Reyataz displaces Kaletra as leading protease inhibitor
  • Despite being the fifth best-selling antiretroviral, Epzicom sales lag behind Truvada

• Unmet needs in HIV
  • The increasing number of treatment-experienced patients achieving undetectable levels suggests efficacy is not an unmet need anymore
  • Resistance remains an issue for first-line NNRTIs and the integrase inhibitors
  • Although antiretroviral tolerability has improved considerably it remains an issue for some drug classes
  • Issue of pill burden eliminated by availability of simplified treatments
  • Cost

• Current level of attainment vs. target product profile

3. R&D APPROACH

• Key findings
• Clinical trial design in HIV
  • Superiority trial design
  • Non-inferiority trial design
  • Dose comparison trial design

• Choice of control arms
• Background regimens
• Duration of studies
• 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 hugely benefited clinical trials
  • Improved understanding of HIV and the advent of HAART have changed endpoints significantly

4. PIPELINE ANALYSIS & FORECASTS: NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

• Key findings
• Overview for nucleoside reverse transcriptase inhibitors
  • Pipeline summary
  • Comparative forecasts

• Apricitabine (Avexa)
  • Drug overview
  • Clinical trial data
  • Clinical and commercial attractiveness
  • SWOT analysis
  • Datamonitor drug assessment score card for apricitabine
  • Satisfaction of unmet needs
  • Forecasts to 2018

• Other drugs in the nucleoside reverse transcriptase class
  • Elvucitabine
  • Amdoxovir

PIPELINE ANALYSIS & FORECASTS: PROTEASE INHIBITORS

• Key findings
• Overview for the protease inhibitor class
• Key early-stage compounds in the protease inhibitor class
  • Pipeline summary

• Marketed protease inhibitors are highly potent and have improved dosing
• Tibotec/Johnson & Johnson developing a co-formulation of Prezista and an investigational pharmacokinetic enhancer
• PPL-100 was previously the most promising among the remaining compounds

PIPELINE ANALYSIS & FORECASTS: NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

• Key findings
• Overview for the non-nucleoside reverse transcriptase class
  • Pipeline summary
  • Comparative forecasts

• Rilpivirine
  • Drug overview
  • Clinical trial data
  • Clinical and commercial attractiveness
  • SWOT analysis
  • Datamonitor drug assessment score card for rilpivirine
  • Satisfaction of unmet needs
  • Forecasts to 2018

• Other drugs in the non-nucleoside reverse transcriptase class
  • RDEA806 (Ardea Biosciences)
  • IDX899 (GlaxoSmithKline/Idenix Pharmaceuticals)
  • Lersivirine (Pfizer)

• Clinical and commercial attractiveness
  • Ardea' s partnering efforts may delay development of RDEA806
  • IDX899 and lersivirine form part of the combined GlaxoSmithKline and Pfizer pipeline

• Forecasts to 2018
• Key early-stage compounds in the non-nucleoside reverse transcriptase class

PIPELINE ANALYSIS & FORECASTS: ENTRY INHIBITORS

• Key findings
• Overview for the entry inhibitors
  • Pipeline summary
  • Comparative forecasts

• Vicriviroc (Schering-Plough)
  • Drug overview
  • Clinical trial data
  • Clinical and commercial attractiveness
  • SWOT analysis
  • Datamonitor drug assessment score card for vicriviroc
  • Satisfaction of unmet needs
  • Forecasts to 2018

• PRO-140 (Progenics)
  • Drug overview
  • Clinical trial data
  • Clinical attractiveness
  • SWOT analysis
  • Datamonitor drug assessment score card for PRO-140
  • Satisfaction of unmet needs
  • Forecasts to 2018

• Other drugs in the entry inhibitor class
  • Ibalizumab
  • PF-232798

• Key early-stage compounds in the entry inhibitor class

PIPELINE ANALYSIS & FORECASTS: INTEGRASE INHIBITORS

• Key findings
• Overview for the integrase inhibitor class
  • Pipeline summary
  • Comparative forecasts

• Elvitegravir (Gilead Sciences)
  • Drug overview
  • Clinical trial data
  • Clinical and commercial attractiveness
  • SWOT analysis
  • Datamonitor drug assessment score card for elvitegravir
  • Satisfaction of unmet needs
  • Forecasts to 2018

• Other drugs in the integrase inhibitor class
  • S/GSK1349572 and S/GSK1265744 (GSK/Shionogi Pharmaceuticals)

• Key early-stage compounds in the integrase inhibitor class

PIPELINE ANALYSIS & FORECASTS: CROSS-CLASS FIXED-DOSE COMBINATIONS

• Key findings
• Overview for the cross-class fixed-dose combinations class
  • Pipeline summary
  • Comparative forecasts

• Truvada/rilpivirine (Gilead and Tibotec/Johnson & Johnson)
  • Drug overview
  • Clinical trial data
  • Clinical and commercial attractiveness
  • SWOT analysis
  • Datamonitor drug assessment score card for Truvada/rilpivirine
  • Satisfaction of unmet needs
  • Forecasts to 2018

• Quad Pill (Gilead Sciences)
  • Drug overview
  • Clinical trial data
  • Clinical and commercial attractiveness
  • SWOT analysis
  • Datamonitor drug assessment score card for cross-class fixed-dose combinations
  • Satisfaction of unmet needs
  • Forecasts to 2018

INNOVATIVE EARLY-STAGE APPROACHES

• Key findings
• Pharmacokinetic enhancers
  • GS-9350 (Gilead Sciences)
  • SPI-452 (Sequoia Pharmaceuticals)
  • PF3716539 (Pfizer/GlaxoSmithKline)

• Microbicides and pre-exposure prophylaxis
  • PRO2000 Gel (Endo Pharmaceuticals)
  • Tenofovir gel (Gilead Sciences)

• The future of HIV treatment
  • Early initiation of therapy
  • Nucleoside-sparing approaches have safety benefits but lack the simplicity of cross-class combinations

BIBLIOGRAPHY

• Journal papers
• Websites
• Others
• Datamonitor reports

APPENDIX

• Methodology
  • Datamonitor forecast methodology
  • Epidemiology forecasts
  • Product forecasts
  • Definition of a standard unit (only use if ForeSight model used to forecast)
  • Datamonitor drug assessment scorecard

• Contributing experts

TABLES

• Table: Products in clinical development for the treatment of HIV infection, 2009
• Table: Sales forecast for pipeline products for the treatment of HIV infection in the US and five major European markets ($m), 2009 - 18
• Table: Leading companies in the HIV market, 2008 - 18
• Table: Gilead Sciences' portfolio assessment for HIV, 2009
• Table: GlaxoSmithKline' s portfolio assessment for HIV, 2009
• Table: Pfizer' s portfolio assessment for HIV, 2009
• Table: GlaxoSmithKline and Pfizer combined marketed portfolio, 2009
• Table: GlaxoSmithKline and Pfizer combined pipeline, 2009
• Table: Prevalence of HIV infection in the seven major markets, 2007
• Table: Mortality rates and life expectancy of HIV patients, stratified by CD4 count, 2008
• Table: HIV incidence, prevalence and mortality from AIDS, by region, 2007
• Table: Leading treatments for HIV infection, 2009
• Table: Atripla - drug profile, 2009
• Table: Target product profile for NRTIs
• Table: Target product profile for NNRTIs
• Table: Target product profile for the Integrase inhibitors
• Table: Target product profile for the entry inhibitors
• Table: Target product profile for cross class combinations
• Table: Key products in the R&D pipeline for the NRTI class, 2009
• Table: Sales forecasts for NRTIs in the US and five major European markets ($m), 2009 - 19
• Table: Apricitabine - drug profile, 2009
• Table: Overview of 48-week efficacy data from AVX-201
• Table: Ability of apricitabine to meet unmet needs
• Table: Sales forecasts for apricitabine in the US and 5EU ($m), 2009 - 18
• Table: Impacting factors on the revenues of apricitabine, 2009 - 18
• Table: Other drugs in the nucleoside reverse transcriptase class, 2009
• Table: Key products in the early-stage R&D pipeline for the protease inhibitor class, 2009
• Table: Key products in the R&D pipeline for non-nucleoside reverse transcriptase inhibitors, 2009
• Table: Sales forecasts for non-nucleoside reverse transcriptase inhibitors in the US and 5EU ($m), 2009 - 18
• Table: Rilpivirine - drug profile, 2009
• Table: A comparison of 48 and 96-week Phase IIb rilpivirine efficacy data, 2009
• Table: An overview of safety findings from the rilpivirine Phase IIb study
• Table: Ability of rilpivirine to meet unmet needs
• Table: Sales forecasts for rilpivirine n the US and 5EU ($m), 2009 - 18
• Table: Impacting factors on the revenues of rilpivirine, 2009 - 18
• Table: Other NNRTIs in clinical development, 2009
• Table: RDEA806 - drug profile, 2009
• Table: Overview of Phase IIa efficacy data
• Table: IDX899 - drug profile, 2009
• Table: Overview of IDX899 Phase IIa efficacy data
• Table: Lersivirine - drug profile, 2009
• Table: Combined sales forecasts for RDEA806, lersivirine and IDX899 in the US and 5EU, 2009 - 18 ($m)
• Table: Impacting factors on the revenues of RDEA806, IDX899 and lersivirine, 2009 - 18
• Table: Key products in the early-stage R&D pipeline for the non-nucleoside reverse transcriptase class, 2009
• Table: Key products in the late-stage R&D pipeline for entry inhibitors, 2009
• Table: Sales forecasts for the entry inhibitors in the US and five major European markets, 2009 - 18
• Table: Vicriviroc - drug profile, 2009
• Table: Overview of 48-week VICTOR-E1 efficacy data
• Table: Overview of safety data from the VICTOR-E1 study
• Table: Ability of vicriviroc to meet unmet needs
• Table: Sales forecasts for vicriviroc in the US and five major European markets ($m), 2009 - 18
• Table: Impacting factors on the revenues of vicriviroc
• Table: PRO-140 - drug profile, 2009
• Table: Sales forecasts for PRO-140 in the US and 5EU ($m), 2009 - 18
• Table: Impacting factors on the revenues of PRO-140, 2009
• Table: Key products in the early-stage R&D pipeline for the entry inhibitors class, 2009
• Table: Key products in the early-stage R&D pipeline for the entry inhibitors class, 2009
• Table: Key products in the late-stage R&D pipeline for the integrase inhibitors class, 2009
• Table: Sales forecasts for integrase inhibitors in the US and five major European markets, 2008 - 18 ($m)
• Table: Elvitegravir - drug profile, 2009
• Table: Sales forecasts for elvitegravir in the US and five major European markets ($m), 2009 - 18
• Table: Other integrase inhibitors in development
• Table: Key products in the early-stage R&D pipeline for the integrase inhibitor class, 2009
• Table: Key cross-class combinations in the late-stage R&D pipeline, 2009
• Table: Sales forecasts for cross-class combinations in the US and five major European markets ($m), 2008 - 18
• Table: Truvada/rilpivirine - drug profile, 2009
• Table: Ability of Truvada/rilpivirine to meet unmet needs
• Table: Sales forecasts for Truvada/rilpivirine in the US and five major European markets ($m), 2009 - 18
• Table: Impacting factors on the revenues of Truvada/rilpivirine, 2009 - 18
• Table: Quad Pill - drug profile, 2009
• Table: Sales forecasts for the Quad Pill in the US and five major European markets, 2009 - 18 ($m)
• Table: Impacting factors on the revenues of the Quad Pill, 2009 - 18
• Table: Datamonitor drug assessment parameters

FIGURES

• Figure: HIV pipeline activity by class, 2009
• Figure: Datamonitor drug assessment summary for antiretroviral therapies in development for HIV infection, 2009
• Figure: HIV market share by company, 2008
• Figure: Estimated number of people living with HIV in the US, 5EU and Japan, 1997 - 2007
• Figure: Estimated number of people living with HIV in the five major European markets, 1997 - 2007
• Figure: Number of newly reported HIV infections and AIDS cases in Japan, 1985 - 2006
• Figure: Estimated Numbers of HIV/AIDS cases among adults and adolescents, by transmission category, 1994 - 2007
• Figure: Number of reported HIV infections by transmission mode, origin and year of notification in the EU/EFTA, 2003 - 07
• Figure: Death rates from HIV infection during pre- and post-HAART era, 1990 - 2003
• Figure: Estimated number of adults (15 - 59 years) living with HIV (both diagnosed and undiagnosed) in the UK, 2007
• Figure: Antiretroviral sales in the US and five major European markets ($m), 2005 - 08
• Figure: Overview of the raltegravir BENCHMRK study
• Figure: Overview of the Phase III study for apricitabine
• Figure: Overview of the Phase IIb study for apricitabine
• Figure: Apricitabine SWOT analysis
• Figure: Datamonitor' s competitive positioning analysis of apricitabine, 2009
• Figure: Overview of the rilpivirine Phase III THRIVE study
• Figure: Overview of the rilpivirine Phase III ECHO study
• Figure: Overview of the rilpivirine Phase IIb study
• Figure: Rilpivirine SWOT analysis, 2009
• Figure: Datamonitor' s competitive positioning analysis of rilpivirine, 2009
• Figure: HIV mechanism of entry into host cell
• Figure: Datamonitor drug assessment summary for products in development for entry inhibitors, 2009
• Figure: Overview of the vicriviroc VICTOR-E3 and VICTOR-E4 studies
• Figure: Overview of the vicriviroc VICTOR-E1 study
• Figure: Overview of the vicriviroc A5211 study
• Figure: Vicriviroc SWOT analysis
• Figure: Datamonitor' s competitive positioning analysis of vicriviroc, 2009
• Figure: PRO-140 SWOT analysis, 2009
• Figure: Datamonitor' s competitive positioning analysis of PRO-140, 2009
• Figure: Overview of the Phase III program for elvitegravir
• Figure: Elvitegravir SWOT analysis, 2009
• Figure: Datamonitor' s competitive positioning analysis of elvitegravir, 2009
• Figure: Datamonitor' s competitive positioning analysis of fixed-dose combinations, 2009
• Figure: Truvada/rilpivirine SWOT analysis, 2009
• Figure: Datamonitor' s competitive positioning analysis of Truvada/rilpivirine, 2009
• Figure: Quad Pill SWOT analysis, 2009
• Figure: Datamonitor' s competitive positioning analysis of the Quad Pill, 2009
• Figure: Datamonitor drug assessment summary of pipeline molecular targeted therapies in development for hematological malignancies, 2007