tb vaccines
DESCRIPTION
By Dr. Ann Ginsberg, VP for Scientific Affairs, AerasTRANSCRIPT
Ann M. Ginsberg, MD, PhD
Aeras and the Global Effort to Develop New TB
Vaccines
J2J Workshop, Kuala Lumpur14 November 2012
DRIVING INNOVATION
Tuberculosis: A Devastating Epidemic
• Over 2 billion people or 1/3 of the world’s population is infected with M. tuberculosis
• Globally, 8.7 million new cases and 1.4 million deaths in 2011
• In SE Asia and Western Pacific, 5.2 million new cases and 610,000 deaths (excluding HIV) in 2011
• Globally, 13% of TB patients are HIV-infected.
• MDR-TB = 3.7% of new cases, globally. XDR-TB identified in 84 countries. Surveillance inadequate in many countries.
3
Number of MDR-TB cases estimated to occur among notified pulmonary TB cases,
2011
XDR-TB: approximately 9% of MDR-TB cases are extensively drug-resistant TB (XDR-TB). As of Oct. 2012, 84 countries had reported at least one XDR-TB case.
The energy and approaches we have put into addressing TB over the
past 20 years have led to insufficient progress.
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Vaccines needed to turn the tide
Source: Christopher Dye, WHO
Global Plan will not eliminate TB by 2050
1
10
100
1000
10000
2000 2010 2020 2030 2040 2050
Year
TB
inc
ide
nc
e/m
illio
n/y
r
Elimination -16%/yr
Global Plan -6%/yr
Current trajectory -1%/yr
Projected incidence in 2050 >100x elimination
threshold
Current trajectory -1.6%/yr
Global Plan - 6%/yr
Elimination - 16%/yr
BCG – current TB vaccine• BCG developed 90 years ago,
not improved upon since.• Most widely delivered
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
− Not recommended for use in infants infected with HIV
− Many genotypes and phenotypes -- multiple BCGs
− Inadequate impact on the global TB epidemic
X
The Need for Improved TB Vaccines
(BCG)
The Potential of New TB Vaccines
New, more effective TB vaccines could:
• 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
Save lives
Break the cycle of transmission
Reduce cost burden to health systems
Increase productivity
A new vaccine
AERAS• Located in Rockville, Maryland, USA, Cape
Town, SA and Beijing, China• Nonprofit research organization operating as
a product development partnership • Mission:
– Develop effective TB vaccines/biologics to prevent TB across all age groups in an affordable and sustainable manner.
• Fully integrated biotechnology organization
13
Regulatory Clearance
Preclinical Development
Discovery Process Development
cGMP Clinical
Manufacture
Clinical Trials Support
Aeras: a Product Development Partnership (PDP)
AERAS
FUNDERS
ACADEMICS
GOVERNMENTS
MANUFACTURERS
CLINICAL SITES
PHARMA/BIOTECH
Collaborating, catalyzing, conducting…
Strategies for TB Vaccine Development
• Pre-infection: to prevent initial or latent infection or disease− Improved priming vaccines− Novel booster vaccines− Infants; LTBI(-)s
Block Initial Infection
Prevent Early Disease
Prevent LatentInfection
Prevent Reactivation
Disease
• Post-infection: to prevent primary +/or reactivation disease
− Novel booster vaccines to extend and enhance immune protection
− LTBI(+) adolescents and adults
• Immunotherapeutic: to improve therapy − Shorten the course of chemotherapy
for active TB or latent TB infection− Improve efficacy of MDR/XDR/TDR-
TB treatment
Global Clinical TB Vaccine Pipeline – 2012
Ad5 Ag85AMcMaster CanSino
VPM 1002Max Planck, VPM,
TBVI
Hybrid-I + IC31SSI, TBVI, EDCTP,
Intercell
Phase II Phase IIIPhase IIbP h a s e I
Immunotherapeutic: Mycobacterial –
whole cell or extract
ID93 + GLA-SE IDRI, Aeras
Hyvac 4/ AERAS-404 + IC31
SSI, sanofi-pasteur, Aeras, Intercell
H56 + IC31SSI, Aeras, Intercell
MVA85A/AERAS-485
OETC, Aeras
AERAS-402/ Crucell Ad35Crucell, Aeras
RUTIArchivel Farma, S.L
Mw DBY, India, M/s.
Cadila
M. VaccaeAnhui Longcom,
China
M72 + AS01GSK, Aeras
MTBVACTBVI, Zaragoza,
Biofabri
rBCG
Viral vector
Protein/adjuvant
Attenuated M.tb
Our Approach
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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.
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Vaccines that prevent adolescents and adults from TB would be the single greatest advance against the disease.
Vaccine – adol/adult
4.2M
There is tremendous momentum in clinical development. Aeras and its global partners are currently testing six candidates in clinical trials.
Aeras partners globally to conduct epidemiological studies and
clinical trials.
Clinical Studies
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TB Vaccine Development:a decade of progress but much more to do
2000 202 2009 2011
2000 2002 2009 2012
No new preventive TB vaccines in clinical trials
1st preventivevaccine enters clinical trials (MVA85A)
1st Phase IIb proof-of-concept of preventive vaccine initiated
15 vaccines have entered clinical trials, 13 currently in clinical trials
• 15 novel TB vaccine candidates have been in clinical trials in the last decade; no “winner” yet
• First human efficacy data expected early 2013 (MVA85A/AERAS-485); major milestone
• Pipeline of 2nd generation candidates, novel vaccine constructs and new delivery platforms continue to be explored
• Substantial challenges remain; solutions will require global partnership and commitment.
• With sufficient resources and positive results from current clinical trials, the first new TB vaccine could be approved within a decade.
Identifying five keys to progress
• Creativity in research and discovery
• Correlates of immunity and biomarkers for TB
vaccines
• Clinical trials – harmonization and cooperation
• Rational selection of TB vaccine candidates
• Building support through advocacy
communications,
and resource mobilization
The TB Vaccine Blueprint
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Keys to Progress
Aeras serves as a catalyst by investing in the world’s most promisingTB vaccine candidates and coordinating a diverse community of global scientists, researchers, governments, and funders on a single mission:the development of effectiveTB vaccines.
Collaboration is key in an unprecedented effort
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Funding and collaboration needed to advance global TB vaccine efforts
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The next phase of new vaccine development is the most critical—
and requires that the global community significantly scale efforts .
This cannot be the work of a single foundation or a small set of
government or biotech partners, but of a much larger global
community.
$78M
2010 global TB vaccine funding
Global Plan annual target
$380M
from TAG Report 2011
Major Contributors
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Aeras Gratefully Acknowledges the Volunteers in Our Clinical Trials, Hard Work of Many Partners including Clinical Trial Sites, and Support of these Major Contributors
Thank You!For more information:
Hello, my name is Mycobacterium tuberculosis! I am the king of the pathogens, killing more people than any other infectious agent except HIVFrom: http://ilovebacteria.com/