Stakeholder Opinions: Tuberculosis - Development pipeline shows signs of life

Table of Contents

EXECUTIVE SUMMARY

• Scope of the analysis
• Datamonitor insight into the Tuberculosis market
• Contributing experts
• Related reports
• Upcoming related reports

DISEASE BACKGROUND

• Disease definition
  • Etiology and symptomatology
  • Pathogenesis

• Management of tuberculosis
  • Vaccination
  • Combination therapy is used to treat tuberculosis

• Industry interest in the antituberculosis therapy market has remained low
  • Public-private partnerships to drive future drug and vaccine development

• Epidemiological trends
  • US
  • Europe
  • Japan
  • Epidemiological trends in Brazil, Russia, India and China and rest of the world

• Drug resistant tuberculosis is a growing problem in high burden countries
• HIV epidemic fueling a rise in tuberculosis cases
• The immigrant population in US and Europe is at high risk

PRESENTATION AND DIAGNOSIS

• Presentation
• Culture and microscopy form the mainstay of tuberculosis diagnosis
  • Cost and access to newer technologies limits uptake in high-burden countries

• Diagnosis of latent tuberculosis infection
  • Tuberculin skin test (TST)
  • Interferon-gamma release assays

• Diagnosis of active tuberculosis infections
  • Laboratory cultures
  • Sputum smear microscopy
  • Nucleic-acid amplification tests
  • Serology
  • Drug susceptibility tests

VACCINATION

• The immune response against tuberculosis
• The current vaccine against tuberculosis: Bacillus Calmette-Guerin
  • BCG vaccine efficacy is highly variable
  • The duration of protection has not been determined
  • BCG vaccination is most commonly practiced in high-burden countries

• Mycobacterial antigens for vaccine development
• Challenges associated with vaccine development
  • Safety
  • HIV infection
  • Late-stage clinical trials
  • Immunization strategies
  • Types of vaccines in development

• Pipeline analysis
  • AERAS-402/Crucell Ad35 (Aeras and Crucell)
  • MVA85A (Aeras, Emergent BioSolutions and the University of Oxford)
  • GSK-692342/AS02 (Aeras and GlaxoSmithKline)
  • Ag85B and ESAT-6 (Intercell AG/Sanofi Pasteur)

• Future outlook for tuberculosis vaccines
  • High-risk groups in seven major markets
  • Supplying public and private sectors in developing countries with TB vaccines

TREATMENT

• Current market overview
• Treatment regimens
  • First line drugs
  • Fixed dose combinations
  • Second-line drugs are required for resistant strains

• Directly Observed Therapy, Short Course (DOTS) programme
• Payment for drugs and services
• Treatment for HIV infected patients
  • Antiretroviral therapy
  • Drug-drug interactions and toxicity
  • Immune reconstitution inflammatory syndrome (IRIS)/paradoxical reactions
  • Sequencing of treatments

• Challenges associated with tuberculosis drug development
  • Complex pathobiology of Mycobacterium tuberculosis
  • Development of drug combinations
  • Long duration of studies

• Unmet needs
  • Multidrug-resistant and extensively drug resistant tuberculosis
  • Increasing patient compliance
  • Tackling latent tuberculosis infection

• Pipeline analysis
  • Fluoroquinolones
  • TMC207 (Tibotec/Johnson & Johnson)
  • Nitroimidazoles
  • SQ109 (Sequella and National Institutes of Health)

BIBLIOGRAPHY

• Journal papers
• Websites
• Other

APPENDIX A

• Contributing experts

APPENDIX B

TABLES

• Table: Prevalence of tuberculosis in the seven major markets, 2006/2007
• Table: Numbers and rates of newly notified tuberculosis patients in Japan, 2005- 07
• Table: Number of multidrug resistant tuberculosis (MDR-TB )cases estimated in the top 10 high burden countries
• Table: Summary of commercial Nucleic Acid Amplification Tests (NAAT) for tuberculosis
• Table: Overview of vaccines in development for prevention and treatment of tuberculosis, 2009
• Table: Overview of Phase II studies for GSK-692342 in tuberculosis
• Table: Overview of drugs in development for treatment of TB
• Table: Overview of clinical trials for gatifloxacin, 2009
• Table: Clinical development program for moxifloxacin for the treatment of pulmonary tuberculosis
• Table: Overview of Phase II clinical trials for TMC207, 2009
• Table: Overview of Phase IIa study for PA-824 in tuberculosis
• Table: Overview of Phase II studies for OPC-67683

FIGURES

• Figure: Estimated number of new cases of tuberculosis worldwide by country, 2006
• Figure: Number of tuberculosis cases and deaths in the US, 1993- 2007
• Figure: Number of tuberculosis cases in the five major European markets, 2002- 06
• Figure: Non-UK born tuberculosis cases by world region of birth in the UK, 2007
• Figure: Total number and rates of newly notified cases of tuberculosis in Japan, 2005- 07
• Figure: Tuberculosis incidence among the 22 high burden countries in 2006
• Figure: Prevalence of tuberculosis per 100,000 population by region and sex in India, 2005- 06
• Figure: Prevalence of medically treated tuberculosis in India, 2005- 06
• Figure: Multidrug resistant tuberculosis (MDR-TB) cases in the US, 1993- 2007
• Figure: Cases of primary multidrug resistant tuberculosis (MDR-TB) in Europe, 2008
• Figure: Estimated HIV prevalence in new tuberculosis cases by country, 2006
• Figure: Geographical distribution of estimated HIV-positive tuberculosis cases, 2006.
• Figure: Trends in tuberculosis cases in US and foreign-born persons in the US, 1987- 2007
• Figure: Percentage of tuberculosis cases of foreign origin in Europe, 2006
• Figure: Advantages and disadvantages of laboratory cultures for tuberculosis testing
• Figure: Advantages and disadvantages of sputum smear microscopy in tuberculosis testing
• Figure: Advantages and disadvantages of nucleic acid amplification tests in tuberculosis testing
• Figure: Overview of the drugs commonly used in treatment of tuberculosis, 2007
• Figure: Timeline of tuberculosis therapy, 1950- 2010
• Figure: Distribution of global antituberculosis therapy sales by region, 2007
• Figure: Volume and value of antituberculosis therapies by molecule type, 2003- 07
• Figure: First- and second-line tuberculosis drug market value by country, 2007
• Figure: Drug targets for Mycobacterium tuberculosis
• Figure: The World Health Organization grouping of first and second-line drugs for the treatment of tuberculosis, 2008
• Figure: Treatment strategies for multidrug-resistant tuberculosis (MDR-TB)
• Figure: Treatment strategies for extensively drug resistant tuberculosis (XDR-TB)
• Figure: Survival over time in the integrated versus the sequential arms in the SAPiT trial