Tuberculosis:
Why Adult Vaccination?
September 4, 2013
Adult Vaccination Workshop

Ann M. Ginsberg, MD, PhD
Chief Medical ...
Tuberculosis: A Devastating Epidemic








WHO declared global public health
emergency
Respiratory infection – i.e...
The Economic Impacts of TB
FAMILY

COUNTRIES

TB primarily strikes down working-age adults

TB costs the global economy an...
TB Incidence by Age

Figure 2. Incidence of TB by age group and gender, Latvia, 2007
TB cases among children constituted 5...
Indoor social networks in a South African township: potential
contribution of location to tuberculosis transmission
HOUSEH...
Failure to Innovate Has Worsened the Epidemic
 Underinvestment in new drugs,
diagnostics and vaccines has led to
growth o...
R&D investments in new tools remain the cornerstone to eliminating TB
within the coming decades
THE NEED FOR A
NEW VACCINE
90-year-old BCG vaccine is the most widely
used vaccine in the world
Reduces the risk of severe pediatric TB disease, but:...
Risk of Infection and Disease
Risk of Infection and Disease – Opportunities for
Vaccination

PREVENT
INFECTION

PREVENT
PROGRESSION
TO ACTIVE
TB

RX

DE...
New vaccines are urgently needed to protect against all
forms of TB, in all age groups, and in all global populations
The Potential of New TB Vaccines
The goal is to deliver new TB vaccines that
would:








Be safer and more effectiv...
Strategies for TB Vaccine Development

Preventive Vaccines: Prime-Boost Regimen

Immunotherapeutic Vaccines: Boost

• Impr...
AERAS
• Not-for-profit

• Mission:
– Developing and advancing TB vaccines
for the world

• Located in Rockville, Maryland,...
Collaboration Is Key

FUNDERS

PHARMA/

ACADEMICS/

BIOTECH

NON-PROFITS

AERAS
CLINICAL
SITES

GOVERNMENTS

MANUFACTURERS...
The Global Pipeline of TB Vaccine Candidates
Phase I

Phase IIa

Ad5 Ag85A
McMaster CanSino

VPM 1002
Max Planck, VPM,
TBV...
Potential World-wide
Health Impact of New TB Vaccines
Potential World-wide Health Impact of New Adult
and Infant TB Vaccines

Immunization of infants, adolescents, adults with ...
TB Vaccine Development:
Highlights for 2013-2014
•

Phase IIb trial of a new vaccine candidate, M72, to begin enrolment

•...
Major Funders and R&D Partners
Thank you.
Thank you.

TB anywhere is TB everywhere/

Advancing Tuberculosis Vaccines for the World
EXPOSED:
A Film Series on Innovation for TB
EXPOSED: A Film Series on Innovation for TB
Advocacy Tool
Each 5-7 minute chapter of this four-part Aeras film series will...
Our Approach

We work with partners to review and prioritize candidates with a goal of advancing at
least two candidates t...
Fully Integrated R&D Capabilities

Preclinical Research

• Staff expertise in vaccine design,
assay development, immunolog...
Key Challenges in TB Vaccine Development

Key Challenges
R&D:
•

Incomplete understanding of TB pathogenesis
and human pro...
Key Challenges
R&D:
•

Possible Approaches

May need multiple vaccines with different

•

mechanisms of action and Target ...
Key Challenges
•

Delivery/market access

Possible Approaches
•

Appropriate TPPs; Innovative platforms;

•

Need low cost...
TB Vaccine Development:
A Decade+ of Progress
2000
No new
2000
preventive TB
vaccines in
clinical trials

2002
1st prevent...
TB Incidence by Age

Globally and regionally, we see some consistent patterns, such as very
low rates in children, in whic...
Indoor social networks in a South African township: potential
contribution of location to tuberculosis transmission

36

R...
TB Incidence by Age

Figure The age- and gender-related incidence of tuberculosis in a hypothetical high
tuberculosis inci...
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Ann ginsberg
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Ann ginsberg

  1. 1. Tuberculosis: Why Adult Vaccination? September 4, 2013 Adult Vaccination Workshop Ann M. Ginsberg, MD, PhD Chief Medical Officer, Aeras
  2. 2. Tuberculosis: A Devastating Epidemic       WHO declared global public health emergency Respiratory infection – i.e., airborne 8.7 million new cases and 1.4 million deaths in 2011; 0.5 million cases, 64,000 deaths in children <15 yrs old Over 2 billion people (1/3 of the world’s population) are infected with M. tuberculosis TB/HIV co-epidemic – TB is leading cause of death for people living with HIV; 13% of TB is in HIV+s MDR/XDR-TB on the rise. XDR-TB identified in 84 countries.
  3. 3. The Economic Impacts of TB FAMILY COUNTRIES TB primarily strikes down working-age adults TB costs the global economy an estimated $1B each day TB is reaching deep into the emerging economies, with country costs, for example, for China estimated to be up to $1.182 trillion from 2006-2015 BUSINESS SECTOR GROWING COST OF DRUG-RESISTANT TB Annual cost to the South African mining sector is over $880 million Cost of treatment for MDR - $12,462 per patient in highest burden countries and $250K in the U.S. Hospitalization for one XDR patient - $483K in the U.S.
  4. 4. TB Incidence by Age Figure 2. Incidence of TB by age group and gender, Latvia, 2007 TB cases among children constituted 5 – 9% out of all new cases during 1998 – 2007 Riekstina V., Sture I., Leimane V., Leimans J. Effective tuberculosis control in the setting of high level anti-tuberculosis drug resistance.EpiNorth,2009;10(3):128-135.
  5. 5. Indoor social networks in a South African township: potential contribution of location to tuberculosis transmission HOUSEHOLD CONTACTS SCHOOL CONTACTS TRANSPORT CONTACTS WORK CONTACTS R Wood et al, PLoSOne, 2012; 7(6):e39246.
  6. 6. Failure to Innovate Has Worsened the Epidemic  Underinvestment in new drugs, diagnostics and vaccines has led to growth of drug-resistant TB  TB evolving, with some strains becoming virtually untreatable  Novel TB vaccines will aim to prevent all strains of TB 7
  7. 7. R&D investments in new tools remain the cornerstone to eliminating TB within the coming decades
  8. 8. THE NEED FOR A NEW VACCINE
  9. 9. 90-year-old BCG vaccine is the most widely used vaccine in the world Reduces the risk of severe pediatric TB disease, but: • • • • Unreliable protection against adult pulmonary TB, which accounts for most TB worldwide Limited impact on the global TB epidemic Not known to protect against latent TB infection Not recommended for use in infants infected with HIV 1920s 2013
  10. 10. Risk of Infection and Disease
  11. 11. Risk of Infection and Disease – Opportunities for Vaccination PREVENT INFECTION PREVENT PROGRESSION TO ACTIVE TB RX DECREASE RECURRENCE RATE/SHORTEN RX
  12. 12. New vaccines are urgently needed to protect against all forms of TB, in all age groups, and in all global populations
  13. 13. The Potential of New TB Vaccines The goal is to deliver new TB vaccines that would:     Be safer and more effective in preventing TB in children, adolescents and adults, including people with HIV 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 Play a crucial role in global efforts to control TB
  14. 14. Strategies for TB Vaccine Development Preventive Vaccines: Prime-Boost Regimen Immunotherapeutic Vaccines: Boost • Improve the prime - recombinant BCG (rBCG) or live Mtb vaccine • Prevent relapse or reinfection following treatment • Develop novel booster vaccines to extend and enhance immune protection • Shorten the course of chemotherapy
  15. 15. AERAS • Not-for-profit • Mission: – Developing and advancing TB vaccines for the world • Located in Rockville, Maryland, USA, Cape Town, SA and Beijing, China • Fully integrated biotechnology organization Discovery Preclinical Development Process Development cGMP Clinical Manufacture Clinical Trials Support Regulatory Clearance 17
  16. 16. Collaboration Is Key FUNDERS PHARMA/ ACADEMICS/ BIOTECH NON-PROFITS AERAS CLINICAL SITES GOVERNMENTS MANUFACTURERS Collaborating, catalyzing, conducting…
  17. 17. The Global Pipeline of TB Vaccine Candidates Phase I Phase IIa Ad5 Ag85A McMaster CanSino VPM 1002 Max Planck, VPM, TBVISII MTBVAC TBVI, Zaragoza, Biofabri H1 + IC31 SSI, TBVI, EDCTP, Intercell ID93 + GLA-SE IDRI, Aeras RUTI Archivel Farma, S.L Crucell Ad35/ MVA85A combo Crucell, Oxford, Aeras Phase IIb MVA85A/AERAS485 Oxford, Aeras Phase III M. Vaccae Anhui Longcom, China M72 + AS01 GSK, Aeras Viral vector rBCG H4/ AERAS-404 + IC31 SSI, sanofi-pasteur, Aeras, Intercell Protein/adjuvant Attenuated M.tb H56/AERAS-456 + IC31 SSI, Aeras, Intercell Immunotherapeutic: Mycobacterial – whole cell or extract Crucell Ad35/ AERAS402 Crucell, Aeras 19
  18. 18. Potential World-wide Health Impact of New TB Vaccines
  19. 19. Potential World-wide Health Impact of New Adult and Infant TB Vaccines Immunization of infants, adolescents, adults with a 60% efficacious vaccine: 90% coverage rate for infants; 20% coverage rate for adolescents and adults CONFIDENTIAL - NOT FOR CIRCULATION DATA ARE ESTIMATES AND SUBJECT TO CHANGE
  20. 20. TB Vaccine Development: Highlights for 2013-2014 • Phase IIb trial of a new vaccine candidate, M72, to begin enrolment • Potential to expand to new countries to conduct clinical trials • New scientific partnerships and collaborations – from research and discovery to clinical trials –focus on enabling biomarker and correlate discovery • Implementation of innovative trial designs – immunotherapy; prevention of infection • New evidence-based tools for advocacy, including modeling cost-effectiveness and public health impact of new TB vaccines 22
  21. 21. Major Funders and R&D Partners
  22. 22. Thank you. Thank you. TB anywhere is TB everywhere/ Advancing Tuberculosis Vaccines for the World
  23. 23. EXPOSED: A Film Series on Innovation for TB
  24. 24. EXPOSED: A Film Series on Innovation for TB Advocacy Tool Each 5-7 minute chapter of this four-part Aeras film series will focus on the personal story of one individual who is working on or would benefit from TB vaccine development, including a TB survivor, a doctor, a clinical trial participant and a researcher. Stories and over 30 interviews from leading TB experts were filmed in the US, the UK, South Africa, India and Malaysia. Ch 1: A Global Epidemic The story of Natalie Skipper, an MDR-TB survivor from Tennessee, is interspersed with expert interviews from around the world to give a sense of the global TB epidemic. Driving Innovation. March 8, 2013 Ch 2: Insufficient Tools This film centers on the story of Dr. Banavaliker, who is struggling to treat patients in India using today’s limited drugs, diagnostics and vaccines, along with expert commentary. Ch 3: The Innovation Movement This chapter details innovation in the fight against TB and follows Unathi, a passionate participant in a clinical trial in South Africa, to show progress in TB vaccine development. Ch. 4: The Last Mile The final chapter will show what is needed to deliver a new TB vaccine for the world and how it could impact the lives of millions, and includes the story of TB vaccine researcher Helen McShane. 27
  25. 25. Our Approach We work with partners to review and prioritize candidates with a goal of advancing at least two candidates to Phase III efficacy trials. With each advance, we collaborate to adjust site capacity, regimens, R&D, and regulatory approaches. TB is complex and may require more than one vaccine to address geographic variations in the strains, stages of the disease, and populations. We continually invest in next-generation candidates, applying lessons learned and fostering novel partnerships and approaches. In collaboration with partners, we evolve and standardize processes to focus on the most promising investigational vaccines. By using scientific approaches including challenge models, systems biology and innovative vaccine designs we accelerate advancement and cut costs. We mobilize resources across public and private entities to sustain the growing costs of TB vaccine R&D efforts as we advance toward the finish line. Only by expanding our network of support and forging new partnerships can we address the immense scientific challenges and global need. AERASDRIVING INNOVATION 28
  26. 26. Fully Integrated R&D Capabilities Preclinical Research • Staff expertise in vaccine design, assay development, immunology, animal studies, antigen selection, platform development, patent and regulatory filings Process Development & Manufacturing • Fully integrated BSL-2 compliant biopharmaceutical manufacturing facility Clinical Research • Network of clinical trial partner sites in North America, Europe, Africa and Asia • Diagnostic and mycobacteriology lab capacity at sites • 25+ clinical trials conducted with multiple candidates and partners • Highly trained and skilled clinical research infrastructure in Rockville, Maryland and South Africa 29
  27. 27. Key Challenges in TB Vaccine Development Key Challenges R&D: • Incomplete understanding of TB pathogenesis and human protective immune response • TB case definition/diagnosis problematic, Possible Approaches • More, innovative, basic research – enhanced investment • Better pediatric diagnostics; adolescent/adult studies • Potential human challenge model (BCG-based): triage candidates early in development. High risk populations • Use Ph IIb/III data to identify/validate animal model(s) and candidate correlates of disease risk and protection especially in infants • Late stage clinical trials are long, large and expensive • No shortcuts for evaluating human efficacy • Multiple animal models; ? predictive ability • No validated correlate(s) of protection 30
  28. 28. Key Challenges R&D: • Possible Approaches May need multiple vaccines with different • mechanisms of action and Target Product • Profiles • Role of non-tuberculous mycobacteria in different geographic settings not clear • Ensure robust pipeline E.g., innate vs. adaptive immunity; CD4+ vs. CD8+ vs. other • Include multiple settings/populations in clinical trials Different proportions of new infection, reinfection and reactivation • Need to address TB in different stages of its life cycle 31
  29. 29. Key Challenges • Delivery/market access Possible Approaches • Appropriate TPPs; Innovative platforms; • Need low cost vaccines for most high Innovative financing mechanisms; Tiered burden countries • pricing Infrastructure doesn’t yet exist for • Start laying groundwork many years in mass campaigns in adults and adolescents • advance; learn from other adolescent/adult vaccines (e.g., HPV, Mening) Multiple manufacturers in high • Start laying groundwork many years in burden regions may be required to advance; partner with regional meet # doses needed for mass manufacturers early campaigns 32
  30. 30. TB Vaccine Development: A Decade+ of Progress 2000 No new 2000 preventive TB vaccines in clinical trials 2002 1st preventive vaccine 202 enters clinical trials (MVA85A) 2009 1st Phase IIb 2009 proof-of-concept of preventive vaccine initiated 2012 15 vaccines have 2011 entered clinical trials, 12 currently in clinical trials • 15 novel TB vaccine candidate have been in clinical trials in the last decade • Robust pipeline of 2nd generation candidates generated • New delivery platforms explored • Capacity and infrastructure development for large-scale trials enhanced in several high burden countries • Epidemiological cohort studies conducted to provide baseline TB incidence datai n several countries 33
  31. 31. TB Incidence by Age Globally and regionally, we see some consistent patterns, such as very low rates in children, in which female notifications are similar or a bit higher then male, followed by an abrupt increase in adolescence with an increasing male/female gap with age. In the Eastern Mediterranean, female notifications surpass male notifications in certain age groups, though it is not known why. 35
  32. 32. Indoor social networks in a South African township: potential contribution of location to tuberculosis transmission 36 R Wood et al, PLoSOne, 2012; 7(6):e39246.
  33. 33. TB Incidence by Age Figure The age- and gender-related incidence of tuberculosis in a hypothetical high tuberculosis incidence community with a large number of children and a low tuberculosis community with a relatively small number of children. 37 Donald P, INT J TUBERC LUNG DIS 8(5):627–629. © 2004 IUATLD

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