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Hope in the TB Pipeline: Vaccines

Hope in the TB Pipeline: Vaccines. Dr. Michael Brennan Senior Advisor, Global Affairs J2J Lung Health Media Training 42nd Union World Conference on Lung Health Lille, France 27 October 2011. WHO Global Tuberculosis Control 2011 Report.

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Hope in the TB Pipeline: Vaccines

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  1. Hope in the TB Pipeline: Vaccines Dr. Michael Brennan Senior Advisor, Global Affairs J2J Lung Health Media Training 42nd Union World Conference on Lung Health Lille, France 27 October 2011

  2. WHO Global Tuberculosis Control 2011 Report • “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 Partnership’s target of eliminating TB by 2050, a transformation in TB prevention, diagnosis and treatment is required.”

  3. This presentation will include… • Why the world needs new TB vaccines • Predicted impact of new TB vaccines • Challenges in TB vaccine development • How the Product Development Partnership model is advancing new TB vaccines • Progress in TB vaccine clinical development • Clinical trial field sites conducting TB vaccine studies • Regulatory capacity • Funding needs to develop TB vaccines that will be affordable and available worldwide

  4. The Tuberculosis PandemicSource: World Health Organization (WHO) 2010 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

  5. The Need for a New TB Vaccine • BCG developed 90 years ago, not improved upon since • Reduces risk of severe pediatric TB disease, but: • Unreliable protection when given to newborns against adult pulmonary TB, which accounts for most TB worldwide • Wide use, but no apparent impact on the growing global TB epidemic • Not known to protect against latent TB • Not recommended for use in infants infected with HIV

  6. The Pathway of TB Infection and Pathogenesis Pulmonary Lung Disease Transmission 10% 90% Reinfection 5% Latent Disease Dissemination

  7. The Pathway of TB Infection and Pathogenesis Pulmonary Lung Disease Transmission Vaccine 10% Vaccine Vaccine 90% Reinfection Vaccine Vaccine 5% Latent Disease Dissemination

  8. Meeting the Public Health Need:Target Populations for TB Vaccines Active Disease Covered by existing vaccine Latently Infected No coverage or impact from existing vaccine Pre-infection Infants Adolescents Adults HIV+ All Ages • 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

  9. TB Epidemiology: Differences in Disease Populations in Different Countries Can Impact Vaccine Approach TB Disease India Primary Infection 62% 19% Re-infection 20% 9% Reactivation 18% 72% * Adapted from Chris Dye, WHO

  10. The Potential of New TB Vaccines A new, more effective TB vaccine could: • Contribute significantly to global efforts to eliminate TB as a public health threat • Be safer and more effective in preventing TB in children, adolescents and adults, including people with HIV (for whom BCG is unsafe) • Protect against all forms of TB – including MDR and XDR • Reduce the cost and burden of TB on patients, health care systems and national economies

  11. Impact of Immunization on Vaccine Preventable Disease Smallpox From: “Understanding Vaccines” USDHHS NIH/NIAID Science Education)

  12. Potential Impact of a 50% Effective Vaccine All age groups 39 & 37% 52% 80% 92% 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

  13. Better TB Vaccines: Reasons for Optimism • 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

  14. Critical Needs in TB Vaccine Field • Advance the pipeline of TB vaccine candidates • Work with partners to market affordable, safe and • effective TB vaccines for all who need them • 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

  15. Aeras’ Mission and the PDP Model • Founded in 2003 with offices in Rockville, Maryland and Cape Town, South Africa • Non-profit biotechnology organization created as a product development partnership • 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.

  16. Aeras Africa OfficeCape Town, South Africa • 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

  17. Pre-clinical Development at Aeras Goal: Choose best vaccine portfolio & facilitate pre-clinical development • Antigen selection • Platform development • Product selection • Process development • Good Laboratory Practice (GLP)/regulatory testing • Animal modeling and immunology • Assay development

  18. Technical Operations at Aeras • Fully integrated biopharmaceutical manufacturing facility • Upstream (fermentation) • 6,000 sq ft completed in 2006 • Downstream (Purification and fill/finish) • 9,000 sq ft. completed in 2009 • Biosafety Level-2 compliant • Meets US and European regulatory standards • Staff expertise in technical operations, quality assurance, and quality control

  19. Foundations Government NGOs Civil Society Academia Pharma & Biotech Industry New Paradigm: Partnership & Collaboration Aeras

  20. TuBerculosis Vaccine Initiative (TBVI) • European efforts to develop more effective, safe vaccines against tuberculosis that will be globally accessible and affordable.   • R&D support and advocacy • Focus: • Discovery • Preclinical • Phase I/IIa - early clinical stages

  21. TB Vaccine DevelopmentA Decade of Progress but much more to do! No new preventive TB vaccines in clinical trials 1st preventive vaccine enters clinical trials (MVA85A) 1st Phase IIb proof-of-concept of preventive vaccine initiated 15 vaccines have entered clinical trials, 12 currently in clinical trials 2000 202 2009 2011 • 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

  22. Currently 12 novel TB Vaccines are in Clinical Trials Phase I Phase II Phase IIb Phase III M72+AS01GSK, Aeras RUTIArchivel Farma VPM 1002Max Planck, Vakzine Projekt Mgmt, TBVI Hybrid-1+IC31SSI, TBVI, EDCTP, Intercell AERAS-422Aeras AdAg85AMcMaster University Hybrid-I+CAF01SSI Hyvac 4/ AERAS-404SSI, Sanofi-Pasteur, Aeras, Intercell\ SSI H56-IC31SSI, Aeras, Intercell, TBVI MVA85A/AERAS-485Oxford-Emergent Tuberculosis Consortium (OETC), Aeras AERAS-402/ Crucell Ad35Crucell, Aeras Mw [M. indicus pranii (MIP)] Dept of Biotechnology (India), M/s. Cadila Prime Boost Post-infection Immunotherapy 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 Source: Tuberculosis Vaccine Candidates – 2010; Stop TB Partnership Working Group on New TB Vaccines With updates from sponsors

  23. Clinical Studies Sponsored by Aeras

  24. Clinical Trial Sites for Phase IIb Proof-of-Concept Trials If successful next step licensing trial to prove effectiveness • MVA85A • 2 Phase IIb trials underway • HIV+ Adults • Infants • Trial Locations • Senegal (HIV+) • South Africa (HIV+, infants) • Partners – Aeras, OETC, EDCTP, MRC, UCT/IIDMM, Laboratoire de Bacteriologie-Virologie du Centre Hospitalier Universitair Aristide Le Dantec • AERAS-402/Crucell Ad35 • 1 Phase IIb trial underway • Infants • Trial Locations • Kenya • Mozambique • South Africa • Uganda (future) • Botswana (future) • Partners - Aeras, Crucell, EDCTP, KEMRI/CDC, CISM, SATVI, NIH

  25. TB Vaccine R & D Manufacturing TB disease and Clinical Trials [Aeras] St. John's National Academy Palamaner, India Cambodian Health Committee Svay Rieng, Cambodia Makerere University Kampala, Uganda KEMRI/CDC Kisumu, Kenya Manhica Health Research Centre Manhica, Mozambique SATVI/U of Cape Town Worcester, South Africa

  26. Regulatory Authorities used in Aeras studies

  27. Regulatory Agency Capacity for Aeras Studies COUNTRIES TB INCIDENCE REGULATORY AGENCY US Very low Very Good Europe Low Very Good South Africa Very High Good Brazil Medium Good India Very High Good China Very High Good Uganda Very High Weak Kenya Very High Weak Botswana Very High Weak Mozambique Very High Weak Senegal Very High Weak Gambia Very High Weak Ethiopia Very High Weak

  28. Collaboration at Trial Sites: Example South Africa • Partnerships with the South African Tuberculosis Vaccine Initiative (SATVI) & The Aurum Institute • Currently conducting clinical trials in infants and HIV+ adults • Most advanced site for large-scale TB vaccine trials in the world • Capacity Development & Utilization • State-of-the-art immunology laboratory • Local staff trained in clinical trial research

  29. Accomplishments in South Africa • Approximately $14 million invested over 7 years to build infrastructure • Additional funding provided by European and Developing Countries Clinical Trials Partnership (EDCTP) • Clinical trials of TB vaccines ongoing in 2009: - 3 Phase I trials - 3 Phase II trials - 1 Phase IIb Proof of Concept trial

  30. Local Benefits of Clinical Research Retain local talent and expertise Raise awareness about TB in the community Support and enhance local clinical research capacity Community health and education Infrastructure remains in the community Leverage investment in infrastructure to use for clinical trials of other diseases

  31. New Partners: Emerging Countries China, India, Brazil, South Africa • Expanding manufacturing capability • Evolving regulatory agency • Improving scientific research • Approving and distributing own products Ready to enter the global stage

  32. Funding Needs 2011-2015$1.9 billion Funding for TB research and development has increased in recent years, reaching US$ 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 2011–2015. - WHO Global Tuberculosis Control 2011 Report

  33. Summary TB Vaccine Development • New TB vaccines could have a significant impact on the global TB epidemic • 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

  34. Conference Sessions Featuring TB Vaccine R&D • October 28 Symposium on “Partnerships to Accelerate TB Vaccine” • 2:30-4:30 pm in Room Rotterdam • 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

  35. Aeras gratefully acknowledges the support of the following major donors and contributors Netherlands Ministry of Foreign Affairs US Food and Drug Administration

  36. Thank You! For more information: www.aeras.org Twitter: @aerasglobaltb Facebook: Aeras Dr. Michael Brennan mbrennan@aeras.org

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