TB Vaccines Development

1. TB Vaccines Development ASEAN-EU STI Cooperation Meeting Thailand Science Park, Thailand 21 -23 January 2014 JAIME C. MONTOYA, MD, MSc, PhD Coordinator, ASEAN-NDI Secretariat Focal Point for the Philippines, ASEAN Subcommittee on Biotechnology Executive Director, Philippine Council for Health Research and Development Department of Science and Technology Professor, University of the Philippines College of Medicine

2. Outline • Global Burden of TB and UN MDG Targets • Status of TB Vaccines Development • ASEAN Initiatives for Vaccine Development ASEAN Flagship Program on Health ASEAN Network for Drugs Diagnostics, Traditional Medicine and Vaccines Innovation • ASEAN Trends in Vaccines Research and Clinical Trials • Goals and Challenges in TB Vaccine R and D

3. Global Burden ofTuberculosis • 8.6 million new cases of TB in 2012 (including 1.1 million cases among people with HIV) • 1.3 million deaths (including 320 000 people with HIV) • TB is one of the world's biggest infectious killers

4. UN MDG TARGETS • By 2015: the global burden of TB disease (disease prevalence and deaths) will be reduced by 50% relative to 1990 levels. • Specifically, this means reducing prevalence to 155 or fewer per 100 000 population, and reducing deaths to 14 or fewer per 100 000 per year by 2015, including people co-infected with TB and HIV. • The number of people dying from TB in 2015 should be less than 1 million.

5. UN MDG TARGETS • By 2050: TB will be eliminated as a global public health problem. • Using the criterion for TB elimination adopted in the USA, this means that the global incidence of TB diseasewill be less than 1 per million population.

6. Tuberculosis vs MDG Targets • Rate of new TB cases has been falling worldwide for about a decade, achieving the MDG global target. • TBincidence rates are also falling in all six WHO regions. • Rate of decline (2% per year) remains slow. • Globally by 2012, the TB mortality rate had been reduced by 45% since 1990. The target to reduce deaths by 50% by 2015 is within reach. Global TB Report 2013

11. Importance of New TB Vaccines • Slow decline of TB incidence globally and the growing problem of MDRTB highlight the critical need for new effective TB vaccines • A TB vaccine for infants with 60% efficacy would contribute to a significant decline in TB incidence by 2050 • An adult TB vaccine with 60% efficacy could potentially avert 30 to 50 million new cases over a 25 year period Global TB Report 2013

12. Strategies for Vaccine Development • Develop a vaccine that will have a higher efficacy than BCG and replace it Improved version of BCG vaccine New attenuated live M. tuberculosis vaccine • Develop a vaccine that primes and boosts protection against TB Global TB Report 2013

16. Priming TB Vaccine

17. Boosting TB Vaccine

32. CONCLUSIONS In these PPD-reactive individuals: • M72/ASO1 Candidate TB Vaccine were well tolerated with comparable reactogenicity as compared to the controls. • A robust and sustainable antigen-specificCD4+ T cellresponses were observed post vaccination with the different antigen and Adjuvant System combinations.

33. CONCLUSIONS In these PPD-reactive individuals: • A vigorous and persistent humoral immune response was observed (data not shown). • The lowest concentration of antigen (10 g of M72) and Adjuvant System (AS01E) will be developed further.

39. Research Priorities Members states were each asked to identify 3 infectious diseases that were of high priority but had received less attention and support for their country. The following diseases were identified: • Dengue • Malaria • Tuberculosis • Japanese encephalitis • Hand, Foot and Mouth

40. The Health R&D Innovation Network in Southeast Asia

41. Why establish a Network? Communicable diseases remain to be the major cause of deaths throughout the world, and this situation is expected to continue Desire to enhance progress in product discovery and development in developing countries and contribute to the implementation of the Global Strategy and Plan of Action (GSPA) on Public Health, Innovation and Intellectual Property approved through the World Health Resolution (WHA61.21) “One ASEAN” by 2015 (ASEAN Secretariat, 2009)

42. Objectives of ASEAN-NDI To establish the capabilities of the ASEAN member countries for drugs, diagnostics, vaccines, and traditional medicine innovation in the areas of infectious tropical diseases, non-communicable diseases, and accidents/traumas To identify gaps and opportunities in the ASEAN To create a database of institutions, networks, and initiatives with capacities for innovation To provide the template for the establishment/future directions of an Asian regional network for innovation in product R&D

43. Vaccines Development Vaccine Number of Institutions Involved in Vaccine Development and Its Different Stages for Each ASEAN Nation

44. Vaccines Research Network in ASEAN countries for vaccines research Source: Elsevier. (2010).Scopus. Retrieved July 2010. Accessed at http://scopus.com/. Notes: Collaborations among top50 most productive institutions (within and outside ASEAN) based on articles on infectious diseases.Size of nodes indicates relative number of articles. Thicker links indicate more instances of collaboration between the two institutions. Blue nodes are institutions in the ASEAN region, while orange nodes represent institutions outside ASEAN. 44

45. Global Trends in Clinical Trials • Traditionally done in relatively wealthy countries in North America, western Europe and Oceania • Now shifting to eastern Europe, Latin America and Asia

47. Drivers of North-South Shift • Need to reduce operational costs while recruiting a large number of patients in a timely manner • Establishment of CROs focused on global clinical trials • Rapid pace of growth of market size • Research capacity and regulatory authority in emerging regions • Harmonization of guidelines for clinical practice and research

48. CLINICAL TRIALS IN THE REGION BY TOPIC Figure.Most clinical trials in the ASEAN region are focused on maladies and conditions other than tropical infectious diseases. Only trials which are currently "open" or "recently completed" in the clinicaltrials.gov database (as of July 2010) were counted. *ClinicalTrials.gov. Data on numbers of clinical trials per country. Retrieved from http://clinicaltrials.gov/. Accessed July 2010.

49. Potential Solutions for R&D Challenges

50. Goals of StopTB -TB Vaccine Initiative 1 . Facilitate preclinical evaluation of candidate vaccines • Develop and promote consensus guidelines, normative references, standardized protocols, experimental models and standardized reagents. • Build capacity at animal testing centres for integration into the WHO preclinical vaccine-testing network. • Facilitate the rapid exchange of information among laboratory and clinical scientists and key Working Group partners.