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.
4. 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.
5. 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.
6. 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.
7. 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
8. R&D investments in new tools remain the cornerstone to eliminating TB
within the coming decades
10. 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
12. Risk of Infection and Disease – Opportunities for
Vaccination
PREVENT
INFECTION
PREVENT
PROGRESSION
TO ACTIVE
TB
RX
DECREASE
RECURRENCE
RATE/SHORTEN
RX
13. New vaccines are urgently needed to protect against all
forms of TB, in all age groups, and in all global populations
14. 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
15. 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
16.
17. 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
21. 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
22. 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
27. 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
28. 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
29. 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
30. 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
31. 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
32. 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
33. 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
34.
35. 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
36. 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.
