hope in the tb pipeline: vaccines (dr. michael brennan)

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Hope in the TB Pipeline: Vaccines Dr. Michael Brennan Senior Advisor, Global Affairs J2J Lung Health Media Training 42nd Union World Conference on Lung Health Lille, France 27 October 2011

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Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

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Page 1: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Hope in the TB Pipeline: VaccinesDr. Michael Brennan

Senior Advisor, Global Affairs

J2J Lung Health Media Training

42nd Union World Conference on Lung HealthLille, France

27 October 2011

Page 2: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

WHO Global Tuberculosis Control 2011 Report

• “Major progress in TB care and control has been achieved since the introduction of the DOTS strategy in the mid-1990s and the launch of its successor, the Stop TB Strategy, in 2006. However, progress is constrained by old technologies. To achieve the Stop TB Partnership’s target of eliminating TB by 2050, a transformation in TB prevention, diagnosis and treatment is required.”

Page 3: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

This presentation will include…

• Why the world needs new TB vaccines• Predicted impact of new TB vaccines• Challenges in TB vaccine development• How the Product Development Partnership model is advancing new

TB vaccines• Progress in TB vaccine clinical development• Clinical trial field sites conducting TB vaccine studies• Regulatory capacity• Funding needs to develop TB vaccines that will be affordable and

available worldwide

Page 4: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

The Tuberculosis PandemicSource: World Health Organization (WHO) 2010

• Global incidence rate = 128 cases/100,000 • 1.4 million TB-related deaths • 8.8 million new cases of TB • 80% of the TB burden is in 22 countries• TB/HIV co-infection and TB drug resistance are key barriers to

progress

Page 5: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

The Need for a New TB Vaccine

• BCG developed 90 years ago, not improved upon since

• Reduces risk of severe pediatric TB disease, but:

– Unreliable protection when given to newborns against adult pulmonary TB, which accounts for most TB worldwide

– Wide use, but no apparent impact on the growing global TB epidemic

– Not known to protect against latent TB

– Not recommended for use in infants infected with HIV

Page 6: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

The Pathway of TB Infection and Pathogenesis

Transmission Pulmonary Lung Disease

Dissemination Latent Disease

90%

10%

5%

Rei

nfe

ctio

n

Page 7: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

The Pathway of TB Infection and Pathogenesis

Transmission Pulmonary Lung Disease

Dissemination Latent Disease

90%

10%

5%

Rei

nfe

ctio

n

Page 8: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Meeting the Public Health Need:Target Populations for TB Vaccines

Pre-infection

Infants Adolescents Adults HIV+ All Ages

Covered by existing vaccine

No coverage or impact from existing vaccine

8

•Target vast, unmet need for new, more effective TB prevention in multiple populations

•Potential replacement and/or boost for widely used BCG:

•180 countries recommend BCG

•100M+ doses per year

Active Disease

Latently Infected

Page 9: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

TB Epidemiology: Differences in Disease Populations in Different Countries Can Impact Vaccine Approach

TB Disease India

Primary Infection 62% 19%

Re-infection 20% 9%

Reactivation 18% 72%

* A

dapt

ed f

rom

Chr

is D

ye,

WH

O

Page 10: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

The Potential of New TB Vaccines

A new, more effective TB vaccine could:

• Contribute significantly to global efforts to eliminate TB as a public health threat

• Be safer and more 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

• Reduce the cost and burden of TB on patients, health care systems and national economies

Page 11: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Impact of Immunization on Vaccine Preventable Disease

From: “Understanding Vaccines” USDHHS NIH/NIAID Science Education)

Smallpox

Page 12: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Potential Impact of a 50% Effective Vaccine

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 LJ, Sabatelli L, Achterberg JT, Sugimoto JD, Longini IM Jr, Dye C, Halloran ME. Epidemiological benefits of more effective tuberculosis vaccines, drugs and diagnostics. Proc Natl Acad Sci USA. 2009;106(33):13980-5

All age groups

39 & 37%

52%

80%92%

Page 13: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Better TB Vaccines: Reasons for Optimism

• Most people (80-90%) do not get disease when infected with Mtb = natural resistance

• Evidence of limited BCG vaccine efficacy in children

• New TB vaccine candidates provide some protection in animals

• New TB vaccines boost immune responses in early human clinical studies

Page 14: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

•A

dva

nce

the

pip

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e o

f TB

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e c

an

did

ate

s

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ork

with

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ract

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trat

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ies

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stin

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ccin

es

Critical Needs in TB Vaccine Field

Page 15: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)
Page 16: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

• Founded in 2003 with offices in Rockville, Maryland and Cape Town, South Africa

• Non-profit biotechnology organization created as a product development partnership

• Public-Private Partnerships with industry, academia, governments, NGOs and others to catalyze product development

• Mission: Develop effective TB vaccines/biologics to prevent TB across all age groups in an affordable and sustainable manner.

Aeras’ Mission and the PDP Model

Page 17: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

• Established in 2008 to focus on Site Development and Epidemiology• Started Clinical Trials Management throughout Africa in 2010• 13 staff members• Expertise in

- Clinical Trials Management- Clinical Data Management and Biostatistics- Laboratory Capacity Development- Clinical Training- Advocacy

• Focus on African collaboration in vaccine development

Aeras Africa OfficeCape Town, South Africa

Page 18: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Goal: Choose best vaccine portfolio & facilitate pre-clinical development

• Antigen selection• Platform development • Product selection• Process development • Good Laboratory Practice

(GLP)/regulatory testing• Animal modeling and

immunology • Assay development

Pre-clinical Development at Aeras

Page 19: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Technical Operations at Aeras

• Fully integrated biopharmaceutical manufacturing facility

• Upstream (fermentation)

– 6,000 sq ft completed in 2006

• Downstream (Purification and fill/finish)

– 9,000 sq ft. completed in 2009

• Biosafety Level-2 compliant

• Meets US and European regulatory standards

• Staff expertise in technical operations, quality assurance, and quality control

Page 20: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

New Paradigm: Partnership & Collaboration

FoundationsGovernmentNGOsCivil Society Pharma &

Biotech Industry

Academia

Aeras

Page 21: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

TuBerculosis Vaccine Initiative (TBVI)

• European efforts to develop more effective, safe vaccines against tuberculosis that will be globally accessible and affordable.  

• R&D support and advocacy

• Focus:– Discovery – Preclinical– Phase I/IIa - early clinical stages

Page 22: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

TB Vaccine DevelopmentA Decade of Progress but much more to do!

2000 202 2009 2011

2000 2002 2009 2011

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, 12 currently in clinical trials

•15 novel TB vaccine candidates have been in clinical trials in the last decade but no “winner” yet

•Robust pipeline of 2nd generation candidates, novel vaccine constructs and new delivery platforms continue to be explored

Page 23: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

AERAS-422Aeras

AdAg85AMcMaster University

Hybrid-I+CAF01SSI

Hyvac 4/ AERAS-404SSI, Sanofi-Pasteur, Aeras, Intercell\

SSI H56-IC31SSI, Aeras, Intercell, TBVI

M72+AS01GSK, Aeras

RUTIArchivel Farma

VPM 1002Max Planck, Vakzine Projekt Mgmt, TBVI

Hybrid-1+IC31SSI, TBVI, EDCTP, Intercell

MVA85A/AERAS-485Oxford-Emergent Tuberculosis Consortium (OETC), Aeras

AERAS-402/ Crucell Ad35Crucell, Aeras

Mw [M. indicus pranii (MIP)]Dept of Biotechnology (India), M/s. Cadila

Phase II Phase IIIPhase IIbPhase I

Source: Tuberculosis Vaccine Candidates – 2010; Stop TB Partnership Working Group on New TB Vaccines

With updates from sponsors

Prime

Boost

Post-infection

Immunotherapy

TB Vaccine TypesViral-vectored: MVA85A, AERAS-402, AdAg85AProtein/adjuvant: M72, Hybrid-1, Hyvac 4, H56rBCG: VPM 1002, AERAS-422Killed WC or Extract: Mw, RUTI

Currently 12 novel TB Vaccines are in Clinical Trials

Page 24: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Clinical Studies Sponsored by Aeras

TB Vaccines Partnerships Clinical Status

Adeno35 with transgene for

85A, 85B & TB10.4

[AERAS-402/Crucell Ad35]

Crucell / Aeras

Ph I adults India

Ph IIb infants S Africa, Kenya, Mozambique

Ph II HIV+ adults S Africa

Modified Vaccinia with 85A

[Oxford MVA85A/AERAS-485]

Oxford / Emergentand Aeras

Ph IIb infants S Africa

Ph IIb HIV+ adults Senegal, S Africa

Fusion protein 85B & TB10.4 in IC31 adjuvant

[HyVac4/AERAS-404]

Sanofi Pasteur/ SSI/Intercell

and Aeras

Ph I adults EU

Fusion Protein M72 in AS02 adjuvant

[GSK M72]

GSK / Aeras Ph II infants Gambia

rBCG with endosome perturbation and over-expression of Mtb antigens

[AERAS 422-rBCG]

Aeras Ph I adults US

Page 25: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Clinical Trial Sites for Phase IIb Proof-of-Concept Trials

AERAS-402/Crucell Ad35

•1 Phase IIb trial underway

•Infants

•Trial Locations

•Kenya

•Mozambique

•South Africa

•Uganda (future)

•Botswana (future)

•Partners - Aeras, Crucell, EDCTP, KEMRI/CDC, CISM, SATVI, NIH

MVA85A

•2 Phase IIb trials underway

•HIV+ Adults

•Infants

•Trial Locations

•Senegal (HIV+)

•South Africa (HIV+, infants)

•Partners – Aeras, OETC, EDCTP, MRC, UCT/IIDMM, Laboratoire de Bacteriologie-Virologie du Centre Hospitalier Universitair Aristide Le Dantec

If successful next step licensing trial to prove effectiveness

Page 26: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

SATVI/U of Cape TownWorcester, South Africa

Makerere UniversityKampala, Uganda

KEMRI/CDCKisumu, Kenya

St. John's National AcademyPalamaner, India

Cambodian Health CommitteeSvay Rieng, Cambodia

Manhica Health Research Centre Manhica, Mozambique

TB

Vac

cin

eR

& D

Man

ufa

ctu

rin

g

TB

dis

ease

an

d C

lin

ical

Tri

als

[Aer

as]

Page 27: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

TB Vaccine Clinical Site Clinical Trial Regulatory Agency

MVA85A/AERAS-485

South Africa Senegal

Phase IIb Phase IIb

MCC CNERS

AERAS-402/Crucell Ad35

US India South Africa Kenya Mozambique Botswana Uganda

Phase I Phase I Phase I; Phase IIb Phase IIb Phase IIb Phase IIb Phase IIb

FDA DCGI MCC KEMRI MoH DRU NDA

SSI/SP H4-IC31 India

Sweden Finland South Africa Switzerland

Phase I Phase I Phase I Phase II Phase I

DCGI MCA FICORA MCC CHUV

AERAS-422 US

South Africa Phase I Phase I

FDA MCC / DAFF

SSI H56-IC31 South Africa Phase 1 MCC

Regulatory Authorities used in Aeras studies

Page 28: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

CO

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Regulatory Agency Capacity for Aeras Studies

Page 29: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Collaboration at Trial Sites: Example South Africa

• Partnerships with the South African Tuberculosis Vaccine Initiative (SATVI) & The Aurum Institute – Currently conducting clinical trials in infants and HIV+

adults

– Most advanced site for large-scale TB vaccine trials in the world

• Capacity Development & Utilization– State-of-the-art immunology laboratory

– Local staff trained in clinical trial research

Page 30: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Accomplishments in South Africa

• Approximately $14 million invested over 7 years to build infrastructure

• Additional funding provided by European and Developing Countries Clinical Trials Partnership (EDCTP)

• Clinical trials of TB vaccines ongoing in 2009:- 3 Phase I trials

- 3 Phase II trials

- 1 Phase IIb Proof

of Concept trial

Page 31: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

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

Page 32: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

New

Par

tner

s: E

mer

gin

g C

ou

ntr

ies

Ch

ina,

In

dia

, B

razi

l, S

ou

th A

fric

a

• Ex

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nd

ing

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nu

fac

turi

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ca

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ty

• Ev

olv

ing

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ry a

gen

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ear

ch

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nd

dis

trib

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ow

n p

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eady

to

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r th

e gl

obal

sta

ge

Page 33: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Funding Needs 2011-2015$1.9 billion

Funding for TB research and development has increased in recent years, reaching US$ 614 million in 2009, but still falls far short of the annual target of US$ 1.8 billion that is included in the Global Plan to Stop TB 2011–2015.

- WHO Global Tuberculosis Control 2011 Report

Page 34: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

• New TB vaccines could have a significant impact on the global TB epidemic

• Tremendous progress is being made in the field of TB vaccine development, with two preventive vaccine candidates now in Phase IIb trials

• GMP manufacturing capacity being developed and manufacturing agreements are being explored with particular emphasis on emerging economies

• Regulatory pathways and market and economic impact research being conducted now to lay the groundwork to accelerate adoption and uptake of new TB vaccines

• Scientific, infrastructure and financial challenges remain; solutions will require global partnership and commitment

• With sufficient resources and positive results for current clinical trials, a new TB vaccine could be available by the end of the decade

Summary TB Vaccine Development

Page 35: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Conference Sessions Featuring TB Vaccine R&D

• October 28 Symposium on “Partnerships to Accelerate TB Vaccine”– 2:30-4:30 pm in Room Rotterdam

• October 28 satellite session on “Synergies in the development of new diagnostics, drugs and vaccines for tuberculosis”

– 4:45-6:45 pm in Room Faidherbe

• Aeras and the TuBerculosis Vaccine Initiative (TBVI) have a booth in the Exhibit Hall (Booth #35) where visitors can learn more about progress in tuberculosis vaccine research and development

Page 36: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Aeras gratefully acknowledges the support of the following major donors and contributors

Netherlands Ministry of Foreign Affairs

US Food and Drug Administration

Page 37: Hope in the TB Pipeline: Vaccines (Dr. Michael Brennan)

Thank You!

For more information:www.aeras.org

Twitter: @aerasglobaltbFacebook: Aeras

Dr. Michael [email protected]