hope in the pipeline the search for new tb vaccines peg willingham aeras global tb vaccine...

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


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)


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.


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


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


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2010 2015 2020 2025 2030 2035 2040 2045 2050Year

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Neonatal pre-exposureNeonate pre-exposure + add effectsPost-exposureMass pre-exposureMass pre-exposure + post-exposure

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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


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


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.


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

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$4 m

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$4 m

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Costs associated with the development of all candidates in Aeras pipeline

Costs related to the development of one TB vaccine candidate


• 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

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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


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


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


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


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


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


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


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 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


Thank You!

For more information:

www.aeras.org

[email protected]

hope in the pipeline the search for new tb vaccines peg willingham aeras global tb vaccine...

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