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J2J Lung Health Media Training 42nd Union World Conference on Lung Health Lille, France 27 October 2011
Major progress in TB care and control has been achieved since the introduction of the DOTS strategy in the mid-1990s and the launch of its successor, the Stop TB Strategy, in 2006. However, progress is constrained by old technologies. To achieve the Stop TB Partnerships target of eliminating TB by 2050, a transformation in TB prevention, diagnosis and treatment is required.
Global incidence rate = 128 cases/100,000 1.4 million TB-related deaths 8.8 million new cases of TB 80% of the TB burden is in 22 countries TB/HIV co-infection and TB drug resistance are key barriers to progress
Reinfection 5%
Latent Disease
Dissemination
Reinfection 5%
Latent Disease
Dissemination
Active Disease
Covered by existing vaccine
Latently Infected
Pre-infection
Infants
Adolescents
Adults
Target vast, unmet need for new, more effective TB prevention in multiple populations Potential replacement and/or boost for widely used BCG: 180 countries recommend BCG 100M+ doses per year
7
Reactivation
18%
72%
Neonatal pre-exposure Neonate pre-exposure + add effects Post-exposure Mass pre-exposure Mass pre-exposure + post-exposure
1600
Incidence per million
1200
800
400
0 2010
Abu-Raddad LJ, Sabatelli L, Achterberg JT, Sugimoto JD, Longini IM Jr, Dye C, Halloran ME. Epidemiological benefits of more effective tuberculosis vaccines, drugs and diagnostics. Proc Natl Acad Sci USA. 2009;106(33):13980-5
Most people (80-90%) do not get disease when infected with Mtb = natural resistance
Evidence of limited BCG vaccine efficacy in children New TB vaccine candidates provide some protection in animals New TB vaccines boost immune responses in early human clinical studies
Evaluate surrogate immune assays and animal models that predict vaccine induced protection
Develop clinical trial site infrastructure and conduct clinical trials Manufacture good manufacturing practice (GMP) lots of TB vaccines Develop regulatory strategies that advance the testing and licensure of TB vaccines
Public-Private Partnerships with industry, academia, governments, NGOs and others to catalyze product development Mission: Develop effective TB vaccines/biologics to prevent TB across all age groups in an affordable and sustainable manner.
Established in 2008 to focus on Site Development and Epidemiology Started Clinical Trials Management throughout Africa in 2010 13 staff members Expertise in - Clinical Trials Management - Clinical Data Management and Biostatistics - Laboratory Capacity Development - Clinical Training - Advocacy Focus on African collaboration in vaccine development
Aeras
Academia
Focus:
Discovery Preclinical Phase I/IIa - early clinical stages
TB Vaccine Development
A Decade of Progress but much more to do!
2000
No new 2000 preventive TB vaccines in clinical trials
2002
1st preventive 202 vaccine enters clinical trials (MVA85A)
2009
1st Phase IIb 2009 proof-of-concept of preventive vaccine initiated
2011
15 vaccines have 2011 entered clinical trials, 12 currently in clinical trials
15 novel TB vaccine candidates have been in clinical trials in the last decade but no winner yet
Robust pipeline of 2nd generation candidates, novel vaccine constructs and new delivery platforms continue to be explored
Phase II
M72+AS01
GSK, Aeras
Phase IIb
MVA85A/ AERAS-485
Oxford-Emergent Tuberculosis Consortium (OETC), Aeras
Phase III
Mw [M. indicus pranii (MIP)]
Dept of Biotechnology (India), M/s. Cadila
AdAg85A
McMaster University
RUTI
Archivel Farma
Hybrid-I+CAF01
SSI
VPM 1002
Max Planck, Vakzine Projekt Mgmt, TBVI
Hyvac 4/ AERAS-404
SSI, Sanofi-Pasteur, Aeras, Intercell\
Hybrid-1+IC31
SSI, TBVI, EDCTP, Intercell
SSI H56-IC31
SSI, Aeras, Intercell, TBVI
Prime TB Vaccine Types Viral-vectored: MVA85A, AERAS-402, AdAg85A Protein/adjuvant: M72, Hybrid-1, Hyvac 4, H56 rBCG: VPM 1002, AERAS-422 Killed WC or Extract: Mw, RUTI Boost Post-infection Immunotherapy
Source: Tuberculosis Vaccine Candidates 2010; Stop TB Partnership Working Group on New TB Vaccines
With updates from sponsors
Partnerships
Crucell / Aeras
Clinical Status
Ph I adults India Ph IIb infants S Africa, Kenya, Mozambique Ph II HIV+ adults S Africa Ph IIb infants S Africa Ph IIb HIV+ adults Senegal, S Africa Ph I adults EU
Fusion protein 85B & TB10.4 in IC31 adjuvant [HyVac4/AERAS-404] Fusion Protein M72 in AS02 adjuvant [GSK M72] rBCG with endosome perturbation and over-expression of Mtb antigens [AERAS 422-rBCG]
Ph II infants Gambia
Aeras
Ph I adults US
Infants
Trial Locations Senegal (HIV+) South Africa (HIV+, infants) Partners Aeras, OETC, EDCTP, MRC, UCT/IIDMM, Laboratoire de BacteriologieVirologie du Centre Hospitalier Universitair Aristide Le Dantec
Infants
Trial Locations Kenya Mozambique
South Africa
Uganda (future) Botswana (future) Partners - Aeras, Crucell, EDCTP, KEMRI/CDC, CISM, SATVI, NIH
St. John's National Academy Palamaner, India Makerere University Kampala, Uganda KEMRI/CDC Kisumu, Kenya Cambodian Health Committee Svay Rieng, Cambodia
South Africa Senegal US India South Africa Kenya Mozambique Botswana Uganda India Sweden Finland South Africa Switzerland US South Africa South Africa
Phase IIb Phase IIb Phase I Phase I Phase I; Phase IIb Phase IIb Phase IIb Phase IIb Phase IIb Phase I Phase I Phase I Phase II Phase I Phase I Phase I Phase 1
SSI/SP H4-IC31
AERAS-422
SSI H56-IC31
TB INCIDENCE
Very low Low Very High Medium Very High Very High Very High Very High Very High Very High Very High Very High Very High
REGULATORY AGENCY
Very Good Very Good Good Good Good Good Weak Weak Weak Weak Weak Weak Weak
Funding for TB research and development has increased in recent years, reaching US$ 614 million in 2009, but still falls far short of the annual target of US$ 1.8 billion that is included in the Global Plan to Stop TB 20112015. - WHO Global Tuberculosis Control 2011 Report
Tremendous progress is being made in the field of TB vaccine development, with two preventive vaccine candidates now in Phase IIb trials
GMP manufacturing capacity being developed and manufacturing agreements are being explored with particular emphasis on emerging economies Regulatory pathways and market and economic impact research being conducted now to lay the groundwork to accelerate adoption and uptake of new TB vaccines Scientific, infrastructure and financial challenges remain; solutions will require global partnership and commitment
With sufficient resources and positive results for current clinical trials, a new TB vaccine could be available by the end of the decade
October 28 satellite session on Synergies in the development of new diagnostics, drugs and vaccines for tuberculosis
4:45-6:45 pm in Room Faidherbe
Aeras and the TuBerculosis Vaccine Initiative (TBVI) have a booth in the Exhibit Hall (Booth #35) where visitors can learn more about progress in tuberculosis vaccine research and development
Aeras gratefully acknowledges the support of the following major donors and contributors
Thank You!
For more information: www.aeras.org Twitter: @aerasglobaltb Facebook: Aeras Dr. Michael Brennan mbrennan@aeras.org