Market Report Source

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

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

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

The NNRTI analogs are dominated by Sustiva and physicians have few choices when drug resistance develops

Despite a large number of available products, two PIs have over half the class market share. The role of PIs in salvage therapy is being redefined 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

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 are living with HIV and AIDS in the USA and Western Europe

Increased HIV diagnosis is driven by immigration, a rise in risky behavior, more convenient diagnostics and broader 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-naïve 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 antiretroviral 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 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 4 HIV PIPELINE ANALYSIS

Pipeline overview

A collaboration between Gilead and BMS has produced Atripla, the first of its kind

Tibotec’s highly anticipated pipeline products set to generate significant revenues for J&J

GSK currently dominates the 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

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-naïve 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

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

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 under investigation

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

Maraviroc

Clinical trial data

Datamonitor analysis

CXCR4 inhibitors

AMD070

Clinical trial data

Datamonitor analysis

Attachment inhibitors

TNX-355

Clinical trial data

Datamonitor analysis

Integrase Inhibitors

MK-0518

Clinical trial data

Datamonitor analysis

GS-9137

Clinical trial data

Datamonitor analysis

Maturation Inhibitors

Bevirimat (PA-457)

Clinical trial data

Datamonitor analysis

Innovative Early-Stage Projects

PRO-140

TRI-999 and TRI-1144

APPENDIX A

Methodology

Datamonitor forecast methodology.

Epidemiology forecasts

Product forecasts

Definition of a standard unit

Estimation of launch dates

Datamonitor drug assessment summary

Contributing experts

Bibliography and Press Releases

Frequently Used Websites

Company websites

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, 2006

Table 5: Overview of number of marketed drugs and developmental drugs for key HIV companies, 2006

Table 6: Overview of currently marketed NRTIs in the six major markets, 2006

Table 7: Overview of NRTI drug pipeline, 2006

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 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, 2006

Table 16: Overview of NNRTI drug pipeline, 2006

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 Protease Inhibitors, 2006

Table 22: Overview of PI drug pipeline and recently launched PIs and pipeline products, 2006

Table 23: RESIST 1 & 2 trial summary

Table 24: Key ongoing clinical trials for Prezista, 2006

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 MK-0518 Phase II trial

Table 35: Overview of MK-0518 Phase II trial

Table 36: Key clinical trials of GS-9137

Table 37: Overview of the Phase I/II study evaluating GS-9137

Table 38: Key clinical trials of PA-457

Table 39: Overview of Phase IIa study evaluating 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 seven major markets, 2003 and 2005

Figure 3: Annual HIV incidence, US, Germany and UK, 1995-2003

Figure 4: HIV-infected individuals accessing treatment in the UK, 1995-2004

Figure 5: HIV incidence by transmission group in Western Europe, 1994-2004

Figure 6: HIV acquired through heterosexual contact in the UK, 1995-2004

Figure 7: Increased ratio of women infected in the seven major markets, 2001 and 2005

Figure 8: Drug resistance by class in newly diagnosed HIV-positive cases in the US, 1995-2004

Figure 9: Drug resistance by class in newly diagnosed HIV-positive cases in the UK, 1996/97-2002/03

Figure 10: Comparison of clinical trials evaluating three drug combinations

Figure 11: Drivers of switching from first- to second-line antiretroviral 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, 1986-2006

Figure 15: HIV virus lifecycle

Figure 16: US quarterly sales of HIV drug classes, 2002-05

Figure 17: Market share within each antiretroviral drug class in the six major markets, 2005

Figure 18: Overview of HIV drug development pipeline, 2006

Figure 19: HIV market share by company, 2005 and 2016

Figure 20: Forecast antiretroviral sales by company, 2016

Figure 21: US quarterly sales of currently marketed NRTIs, 2002-2005

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, 2006

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, 2006

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 BILR-355

Figure 39: BILR355 sales forecast, 2006-2016

Figure 40: Unmet needs in the Protease Inhibitor class, 2006

Figure 41: Mutations in the protease gene associated with resistance to PIs

Figure 42: SWOT Analysis for Aptivus