hope in the tuberculosis pipeline iii: vaccines

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Hope in the TB Pipeline II: Vaccines

Peg Willingham

Aeras Global TB Vaccine Foundation

J2J Lung Health Media Training41st Union World Conference on Lung Health

Berlin, Germany

12 November 2010



AERAS GLOBAL TB VACCINE FOUNDATION

Existing TB Vaccine Ineffective

BCG unreliable against pulmonary TB, whichaccounts for most TB disease worldwide

BCG is not know to protect against latent TB

BCG is not recommended for use in infantsinfected with HIV - increased risk for severeBCG-related complications

Despite wide use, BCG has had no apparentimpact on the growing global TB epidemic

BCG does reduce risk of severe pediatric TBdisease, so it should continue to be useduntil a better TB vaccine is available

BCG introduced in 1921




Tuberculosis: TB Vaccine TooDangerous for Babies With AIDS

Virus, Study Says

J uly 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 publishedby the World Health Organization. It

recommended that vaccination be delayed until

babies can be tested.




WHO 2007 Recommendations on BCG

Children with HIV infectionregardless of symptoms should notbe BCG vaccinated

All high risk infants need HIVscreening ± Maternal antibody masks antibody

tests

± Detection of virus required

± Very difficult to implement in manyplaces

Disseminated BCG in HIV infected infants recently (2009) estimatedto be 992 per 100,000 (Hesseling, et al)



AERAS GLOBAL TB VACCINE FOUNDATIONPredicted Impact of 50% Effective

New TB vaccine

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Goals for Better TB Vaccines

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 (for whom BCG is unsafe)

Protect against all forms of TB ±

including MDR and XDR




TuBerculosis Vaccine Initiative TBVI

European efforts to developmore effective, safe vaccinesagainst tuberculosis, that will

be globally accessible andaffordable.

R&D support and Advocacy

Focus: ± Discovery

± Preclinical

± Phase I/IIa - early clinical stages




Aeras Global TB Vaccine Foundation

MissionTo develop new, more effective TBvaccines and ensure their availability toall who need them

Method Non-profit PDP; collaborate with

academic, biotech, pharma and NGOpartners to develop and test new TBvaccines

Pursue a Prime-Boost strategy by

developing a modern replacement for BCG plus booster vaccines

Develop vaccines in our own lab andmanufacturing plant



AERAS GLOBAL TB VACCINE FOUNDATIONTB Vaccine Pipeline

VPM 1002Max Planck, Vakzine

Projekt Mgmt, TBVI

rBCG30* UCLA, NIH, NIAID,

Aeras

AdAg85A

McMaster University

Hybrid I+CAF01SSI

Hyvac AERAS 0SSI, Sanofi-Pasteur,

Aeras, Intercell

RUTI Archivel Farma

M smegmatis*

Hybrid I+IC 1SSI, TBVI,

Intercell

M72GSK, Aeras

MVA85AAERAS 85Oxford-Emergent

Tuberculosis

Consortium

(OETC), Aeras

AERAS 02Crucell Ad 5Crucell, Aeras

M vaccae* Immodulon, NIH

Preclinical Phase II Phase IIIPhase IIbPhase I

* indicates candidates that have been in clinical trials in the past, but are not currently being tested in clinical trials

Source: Tuberculosis Vaccine Candidates ± 2009; Stop TB Partnership Working Group on New TB Vaccines

As of November 2009

AE

RAS 22 Aeras

Mtb [¨lysA ̈panCD¨secA2] Albert Einstein College

of Medicine

MTBVAC01 [ ̈phoP,

¨fad D26 ]University of Zaragoza,

Institute Pasteur,

TuBerculosis Vaccine

Initiative (TBVI)

HBHAInstitute Pasteur of

Lille, INSERM, TBVI

Hybrid 56Statens Serum Institute

(SSI), Aeras, Intercell,

TBVI

HG85 A BShanghai H&G Biotech

Prime

Boost

Post infection

Immunotherapy

P reclinical vaccine candidates are not yet in clinical trials, but have been manufactured under Good Manufacturing Practice

(GMP

) for clinical use and have undergone some preclinical testing that meets regulatory standards.




12 candidates have entered clinical trials; 9 currentlybeing tested; 10th will enter trials this year

Robust pipeline of candidates in preclinical development

Capacity and infrastructure developed or being

developed at several sites, including South Africa,Kenya, Uganda, Mozambique, Ethiopia, Senegal andthe Gambia

Manufacturing capacity being developed andagreements explored, with particular emphasis on

emerging economies Regulatory pathways and market/economic impact

research laying groundwork to accelerate adoption anduptake of new TB vaccines

Progress in TB Vaccine Development




Approach to a New TB Vaccine

Improve BCG ± make a

recombinant rBCG

Prime-Boost regimen

Give booster vaccinations in

infants

Give booster vaccinations in

adolescents who have received

BCG at birth



Aeras TB Vaccine Candidates in Clinical Trials

Potential Boost Vaccines

All vaccine candidates found to have acceptable safety profiles All candidates induced CD4+ and/or CD8+ T-cell responses to TB

antigens

Immunogenicity results of booster candidates after BCG-priming areencouraging for post-BCG prime-boost strategy

SSI HyVac4 / AERAS-404 Status: Phase I

Recombinant protein vaccine intended to be a booster vaccine

Phase I clinical trials being conducted in Europe and Africa

GSK M72 Status: Phase II

Recombinant protein vaccine intended to be a booster vaccine

Phase I and II trials conducted in Europe, Africa and Asia, including a Phase I trial in HIV+ inEurope

AERAS-402 / Crucell Ad35 Status: Phase IIb

Viral vectored vaccine utilizing adenovirus 35; intended to be a booster vaccine

Phase I and II trials conducted in North America and Africa; Phase IIb recently initiated in HIV+ inS. Africa

MVA85A / AERAS-485 Status: Phase IIbViral vectored vaccine utilizing modified vaccinia Ankara; intended to be a booster vaccine

The most clinically-advanced booster vaccine for tuberculosis with an ongoing proof-of-conceptPhase IIb trial in infants

Previous clinical trials in the UK and Africa, including in HIV+

Awarded orphan drug status by EMEA




Clinical Trials: Field Site Development

Large-scale community-based clinicaltrials are conducted in high burdencountries

Aeras partners with local researchinstitutions to establish field sites andconduct clinical research

Build local infrastructure and healthcare/research capacity to perform futureGood Clinical Practice (GCP) compliantPhase III clinical trials



AERAS GLOBAL TB VACCINE FOUNDATIONAeras Partnerships for Field Research

SATVI/UCT, Aurum Institute,UCT Lung Institute, South Africa

Makerere University, Uganda KEMRI/CDC, Kenya

St Johns Research

Institute, India Cambodian HealthCommittee, Cambodia

Manhica Health Research Centre

Mozambique



AERAS GLOBAL TB VACCINE FOUNDATIONSite Development

South Africa Partnership with South African Tuberculosis Vaccine Initiative (S ATVI)

Field site developed in Worcester (~120 km from Cape Town); most

advanced site in the world for TB vaccine trials

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- ³Reach for the Stars´) ± over

230 staff trained since 2004

± Resource Center



AERAS GLOBAL TB VACCINE FOUNDATIONAeras Sponsored Trials

in South Africa

SATVI is conducting Phase I, II and

IIb studies of four vaccine candidates

in Worcester

UCT Lung Institute conducted aPhase II clinical trial in adults with

active or previous TB in Cape Town

Aurum Institute is enrolling adults

living with HIV in Phase IIb trial in

Klerksdorp (mining community)



AERAS GLOBAL TB VACCINE FOUNDATIONKey Accomplishments at Other

Partner Sites State-of-the-art immunology and

mycobacteriology laboratory established in India

Mycobacterial lab capacity is being augmented inKenya and Uganda

Local staff trained in clinical research in Kenya,

Uganda and India Epidemiological cohort studies in Cambodia,

India, Kenya and Uganda

Quality management and data managementinfrastructure developed in India and Uganda

New state-of-the-art Clinical Research Center established at a District Hospital in western Kenya

First multicenter TB vaccine clinical trial initiated inKenya




Local Benefits of 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



Access and Availability

Future access considered at every stage of vaccinedevelopment

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 country governments

± International organizations (GAVI, UNICEF)

± Developing country partners




Demand from Endemic Countries

Market study to analyze acceptability of 3

new pre-exposure vaccine scenarios

86 respondents ± govt., providers, NGOs

Interviews conducted in 8 high TB burden

countries: Brazil, Cambodia, China, India,

Mozambique, Romania, Russia, South

Africa




Drivers of Future Uptake

Wide recognition that TB is serious andneglected problem; MDR-TB threat

Widespread dissatisfaction with current BCG

Likely demand for partially effective vaccinebetter than BCG

Willingness to commit to rapid introduction

FD A or EME A approval will speed adoption

Willingness to spend money out of existingbudgets for prime-boost; private sector




Barriers to Future Uptake

Clarify expected benefits (20-30 years)

Fatalism about TB ± lack of political will

and competing priorities, e.g., HIV/AIDS

Waiting for strong efficacy data, especially

in own country

Some resistance to adolescent boosting

(transient populations)

Some skepticism about aerosol delivery




Lessons Learned

Heterogeneity of responses within and between

countries

Strong efficacy data will be a critical success

factor for introduction, including in-country data Cost, if kept low, not likely to be major issue; not

an issue in private markets

Education and preparation will be necessary, but

raising awareness and expectations too high

needs to be avoided



AERAS GLOBAL TB VACCINE FOUNDATIONJoin Us for a TB Vaccine Press Briefing

³ Eliminating TB: the promise of new TB vaccines´

WHAT: An update on the state of TB vaccinedevelopment, outcomes from the recent global sciencemeeting on TB vaccines, and plans for the future.

WHO: ± Kenyan TB Advocate Lucy Ghati

± Dr. Joris Vandeputte, TBVI

± Dr. Lew Barker, Aeras

WHERE: Press Briefing Room 42

WHEN: 10 am - Monday, 15 November




Aeras gratefully acknowledges the

support of the following major donors

Netherlands Ministry of Foreign Affairs

US Food and Drug Administration




Thank You!

For more information:

www.aeras.org

[email protected]

hope in the tuberculosis pipeline iii: vaccines

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