Upload
emma-byrd
View
218
Download
0
Tags:
Embed Size (px)
Citation preview
Hope in the Pipeline
The Search for New TB VaccinesPeg Willingham
Aeras Global TB Vaccine Foundation
“Journalist to Journalist”National Press Foundation
December 4, 2009Cancun, Mexico
AERAS GLOBAL TB VACCINE FOUNDATION
By Calmette & Guérin
1908-1921
No new TB vaccine in almost 90 years
Invention of Bacille Calmette-Guérin (BCG) Vaccine
AERAS GLOBAL TB VACCINE FOUNDATION
BCG Vaccine Efficacy
• BCG is one of the most widely used vaccines in the world, yet TB remains the second leading cause of infectious disease deaths
• Prevents some severe forms of TB in children, saves 40,000 to 70,000 children a year
• Fails to prevent pulmonary tuberculosis, the most common form, and TB in adults (nearly two million people die each year)
AERAS GLOBAL TB VACCINE FOUNDATION
Tuberculosis: TB Vaccine Too Dangerous for Babies With AIDS
Virus, Study Says
July 2, 2009 – The vaccine against tuberculosis that is routinely given to 75 percent of the world’s infants is too risky to give to those born infected with the AIDS virus, says a new study published by the World Health Organization. It recommended that vaccination be delayed until babies can be tested.
AERAS GLOBAL TB VACCINE FOUNDATION
WHO Guidance on BCG
• World Health Organization (WHO) changed guidelines in 2007
• BCG is not recommended for infants known to be infected with HIV, due to increased risk of disseminated BCG disease (one percent of infants with HIV who receive the vaccine get disseminated BCG, 75 percent die)
• Difficult to implement in practice
AERAS GLOBAL TB VACCINE FOUNDATION
Potential of a New TB Vaccine
• Eliminate TB as a public health threat, in line with global targets (<1 case/million), in conjunction with new drugs and diagnostics
• Safe and 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
AERAS GLOBAL TB VACCINE FOUNDATION
Blo
ck I
nit
ial
Infe
ctio
n
Pre
ven
t E
arly
D
isea
se
Pre
ven
t L
aten
tIn
fect
ion
Pre
ven
t R
eact
ivat
ion
Dis
ease
AERAS GLOBAL TB VACCINE FOUNDATION
TB (all types) Incidence
0
400
800
1200
1600
2000
2010 2015 2020 2025 2030 2035 2040 2045 2050Year
Inci
den
ce p
er m
illio
n
Neonatal pre-exposureNeonate pre-exposure + add effectsPost-exposureMass pre-exposureMass pre-exposure + post-exposure
Abu-Raddad, Sabatelli, Achterberg, Sugimoto, Longini, Dye and Halloran
All
age
gro
up
s
*Pre
-exp
osu
re v
acc
ine
with
ad
diti
on
al e
ffe
cts
tha
t re
du
ce t
he
life
time
ris
k o
f d
eve
lop
ing
dis
ea
se in
slo
w p
rog
ress
ors
by
ha
lf to
ab
ou
t 2
.5%
an
d t
he
infe
ctio
usn
ess
of
the
sm
ea
r-p
osi
tive
an
d s
me
ar-
ne
ga
tive
ca
ses
by
ha
lf.
*
AERAS GLOBAL TB VACCINE FOUNDATION
Aeras Global TB Vaccine Foundation
MissionTo develop new, more effective TB vaccines and ensure their availability to all who need them
Goals• A more effective, safe and
affordable TB vaccine by 2016• Identify correlates and
surrogate markers of vaccine induced protection
• Develop second generation TB vaccines with increased potency and broader protection
AERAS GLOBAL TB VACCINE FOUNDATION
IndustryGlaxoSmithKline Biologicals, Belgium
Crucell, the Netherlands Statens Serum Institute, Denmark ImmunoBiology, United Kingdom
Wuhan Institute of Biological Products, ChinaSerum Institute, India
Thymed, GermanyJapan BCG Laboratory, JapanKorean Institute of TB, Korea
Cyncron, DenmarkImmune Solutions, New Zealand
Sanofi Pasteur, FranceSmittskyddsinstitutet, SwedenEmergent BioSolutions, U.S.
Intercell, Austria
Foundations/Governments/
NGOsBill & Melinda Gates Foundation, U.S.Ministry of Foreign Affairs of Denmark
The Netherlands Ministry of Foreign Affairs, the Netherlands
Fogarty International Center and NIAID, National Institutes of Health, U.S.
Research Council of Norway, NorwayMaryland Department of Business and
Economic Development, U.S.AIDS Fondet, Denmark
Cambodian Health Committee, CambodiaEuropean and Developing Countries Clinical
Trials Partnership (EDCTP), European Commission
LHL/ The Norwegian Association of Heart and Lung Patients, Norway
Planeta Salud, SpainMary Lynn Richardson Fund, U.S.Manhiça Health Research Centre,
MozambiqueMedicine in Need (MEND), U.S.
Stop TB Partnership, SwitzerlandTB-Alert, United Kingdom
Wellcome Trust, United Kingdom
AcademiaOxford University, United Kingdom
South African TB Vaccine Initiative (SATVI), South AfricaSt. Johns Research Institute, India
Makerere University, UgandaKenya Medical Research Institute, Kenya
Karolinska Institute, Sweden Wuhan University, China
Albert Einstein College of Medicine, U.S. Arizona State University, U.S.Aurum Institute, South Africa
Biomedical Primate Research Center, the NetherlandsCase Western Reserve University, U.S.
Centre for International Health, University of Bergen, NorwayColorado State University, U.S.
Emory University, U.S.Food and Drug Administration, U.S.
Foundation for Innovative New Diagnostics (FIND), Switzerland Harvard University, U.S.
International AIDS Vaccine Initiative (IAVI), U.S.Johns Hopkins University, U.S.
KNCV Tuberculosis Foundation, the NetherlandsLeiden University Medical Center, the Netherlands
Life Science Research Israel (LSRI), IsraelMax Planck Institute for Infection Biology, Germany
National Cancer Institute (NKI), the NetherlandsOregon Health Sciences University, U.S.
Stanford University, U.S. Saint Louis University., U.S.
Tuberculosis Vaccine Initiative (TBVI), EuropeTulane University, U.S.
University of California-San Francisco, U.S.University of California-Los Angeles, U.S.University of Maryland, College Park, U.S.
University of Tampere, FinlandUniversity of Wales, United Kingdom
Vanderbilt University., U.S.Walter Reed Army Institute of Research, U.S.
Aeras Global Vaccine Development PartnersAeras
Foundations/Government/NGOs
Industry
Academia
AERAS GLOBAL TB VACCINE FOUNDATION
TB Vaccine Pipeline
Additional research at the discovery/early pre-clinical level: Bhagawan Mahavir Medical Research Center; Cardiff University; EpiVax, Inc.; ImmunoBiology Ltd.; Infectious Disease Research Institute; Institute de Pharamacologie, Puso; Karolinska Institute; Malaysia-Finlay Institute, NIAID; NIH; Osaka University; Shanghai H&G Biotech; Sequella; UCLA; and, Vanderbilt University .
Vaccine Candidate Pre-Clinical Phase I Phase II Phase IIb Phase IIIAERAS402/Crucell Ad35Crucell N.V./Aeras
MVA85A/AERAS-485OETC/Aeras
GSK M72GSK Biologicals/Aeras
Hybrid 1 SSI IC-31SSI, TBVI, Intercell
HyVac4/AERAS-404sanofi pasteur/SSI/Intercell/Aeras
VPM 1002Max Planck/Vakzine Projekt Management GmbH/TBVI
AdAg85AMcMaster University
RUTIArchivel Farma, S.I.
Hybrid 1 SSI CAF01SSI
AERAS-rBCGAeras
AERAS-CapsidAeras
Other rBCG rMtbAlbert Einstein S. of Med., Institute Pasteur, Univ. of Zaragoza, TBVI
AERAS-other virusAeras
Protein/PolysaccharidesInst. Pasteur de Lille/Inserm, Albert Einstein S. of Med., Aeras, Karolinska Instit.
AERAS GLOBAL TB VACCINE FOUNDATION
Challenge Models ($1 million per year for 7 yrs)
TB Vaccine Development TimelineField Site Development ($2-4 million per yr, per site for 7 yrs)
2.5 Years 2 Years 4 Years
$160 Million
• 4
of A
eras
’ 6
TB
vac
cin
e ca
nd
idat
es a
re in
cli
nic
al t
rial
s in
Afr
ica;
th
e ot
her
s ar
e ex
pec
ted
to
ente
r tr
ials
in 2
010
• $1
60 m
illi
on t
o co
nd
uct
a P
has
e II
I li
cen
sure
tri
al o
f on
e ca
nd
idat
e
• W
ith
su
ffic
ien
t re
sou
rces
, a n
ew T
B v
acci
ne
cou
ld b
e re
ady
by
2016
• T
he
Tre
atm
ent
Act
ion
Gro
up
est
imat
ed a
$1.
5 b
illi
on f
un
din
g ga
p
for
TB
res
earc
h f
or 2
008
alon
e
1 -
2 Y
ears
1 Y
ear
Vaccine Discovery
Pre-Clinical
Testing
Phase I
Phase II
Ph
ase
IIb
Ph
ase
III
Manufacturing ($5 million per yr for 9 yrs)
$2.5
mil
lio
n
$4 m
illi
on
$4 m
illi
on
Lic
ensu
re
$1.5
mil
lio
n
Costs associated with the development of all candidates in Aeras pipeline
Costs related to the development of one TB vaccine candidate
AERAS GLOBAL TB VACCINE FOUNDATION
• Safer in HIV infected infants or others with immune-suppression
• BCG or rBCG boosted with another TB vaccine is much better than either vaccine alone
• Constructed to over-express antigens from each stage of the TB life cycle
• Prevent infection and reactivation utilizing “prime-boost” regimens
• A new vaccine candidate with all of these properties is expected to enter clinical trials in 2010
Rec
om
bin
ant
BC
G (
rBC
G)
- A
Bet
ter
BC
G
AERAS GLOBAL TB VACCINE FOUNDATION
Aerosol Delivery of New TB Vaccines
• Very small particles (2-4 microns) get deep into the lung, where infection occurs
• Aerosol delivery may provide an easy, affordable delivery mechanism that could eliminate the need for needles and cold chain and provide superior protection
Spray Drying
AERAS GLOBAL TB VACCINE FOUNDATION
Example of Site Development: South Africa• Partnership with South African Tuberculosis Vaccine
Initiative (SATVI)• Field site developed in Worcester (~120 km from Cape
Town)• Infrastructure developed:
– State-of-the-art immunology laboratory – Highly skilled staff capable of performing the duties
necessary to maintain the infrastructure and execute clinical research
– Clinical and office facilities– Professional Development Program (Siyantinga-
“Reach for the Stars”) – program initiated in 2001– Resource Center established in 2005
AERAS GLOBAL TB VACCINE FOUNDATION
Accomplishments in South Africa
• South African Tuberculosis Vaccine Initiative - Most advanced site for large-scale TB vaccine trials in the world
• BCG randomized clinical trial of 11,680 infants
• Cohort studies involving more than 11,500 infants and adolescents
• Conducting Phase I and Phase II studies of 4 vaccine candidates, first Phase IIb preliminary efficacy study of a new TB vaccine in infants in 80 years
• 231 staff trained since 2004, including 162 female staff
• Establishment of a Quality Management System and data capture mechanism
AERAS GLOBAL TB VACCINE FOUNDATION
Capacity Building Highlights at Other Sites
• State-of-the-art immunology and mycobacteriology lab developed in India - first of its kind in the area
• State-of-the-art lab and case verification ward opened in Uganda
• Quality management and data management infrastructure developed in India and Uganda
• Professional Development Programs
• Phase I trial at Kenya site• Planned multi-country Phase II trials
AERAS GLOBAL TB VACCINE FOUNDATION
Benefits of Site Development and 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
AERAS GLOBAL TB VACCINE FOUNDATION
Vaccine Efficacy Trials
MVA85A/AERAS-485• First efficacy trial of a new
TB vaccine in infants in more than 80 years
• 2,800 infants• In collaboration with
SATVI, Oxford-Emergent Tuberculosis Consortium and Wellcome Trust
Additional Proof-of-Concept Studies Planned for 2010
AERAS GLOBAL TB VACCINE FOUNDATION
Novel Approaches to Manufacturing
Building manufacturing capacity and partnerships now to:•Reduce the cost and time to manufacture and deliver vaccines to all who need them
•Produce enough bulk doses of vaccine to meet the world’s estimated need
•Work with partners in countries such as India, China, Korea and South Africa to produce, fill, finish and distribute vaccines at the lowest possible price
•Ensure uniformity of quality
•Minimize lag time between licensure and distribution
AERAS GLOBAL TB VACCINE FOUNDATION
Access and Availability• Future access considered at every stage of vaccine
development • Manufacturing
– Guarantee by partners for sufficient production and affordable prices, or technology transfer
– Manufactured by Aeras with partners in developing world– Aeras will not consider vaccine candidates that will be costly to
manufacture on a large scale • Pricing
– Dual pricing for affordable distribution in resource-poor countries– Cost plus purchase from partner– Aeras provides at cost
• Distribution– Developing world governments– International organizations (GAVI, UNICEF)– Developing world partners
AERAS GLOBAL TB VACCINE FOUNDATION
Aeras gratefully acknowledges the support of the following major donors
Net
herla
nds
Min
istr
y of
For
eign
Affa
irs
Min
istr
y of
For
eign
Affa
irs o
f Den
mar
k
THE MARY LYNN RICHARDSON
FUND