TB and HIV/AIDS (Peg Willingham)

8/7/2019 TB and HIV/AIDS (Peg Willingham)

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TB & HIV/AIDS

Peg Willingham, Senior Director for External Affairs

Aeras Global TB Vaccine Foundation

JOURNALIST to JOURNALISTGlobal Media Training Program on HIV/AIDS

Vienna, AustriaJuly 15, 2010


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AERAS GLOBAL TB VACCINE FOUNDATION

The Tuberculosis Pandemic

TB is spread froman infectiousperson to avulnerable person

through the air

TB usually affectsthe lungs (80% ofcases) but canaffect any part ofan infected person


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The TB Pandemic

The World Health Organization (WHO)

estimates that in 2008:

9.4 million new cases of TB were

diagnosed

1.8 million people died from TB

One out of three people in the world havebeen infected with TB (although most do

not develop disease)


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Estimated TB Incidence Rate, 2007

Estimated new TB cases (all

forms) per 100 000 population

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health

Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.WHO 2009. All rights reserved

No estimate

0-24

50-99

>= 300

25-49

100-299


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The TB Pandemic

TB is the worlds 2nd most deadly infectious disease in

adults, after HIV/AIDS, and one of leading causes of

death globally.

TB is curable, but treatment is lengthy often spanning

6 months to a year and is not available to all.

Drug-resistant TB is expensive, even more lengthy,

and difficult.


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What Drives the TB Epidemic?

Poverty

Malnutrition

Overcrowded livingconditions

Slums 1 billion and growing

Smoking Diabetes

HIV


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No estimate

04

2049

>= 50

519

HIV prevalence in

TB cases, (%)

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health

Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.

WHO 2009. All rights reserved

HIV Prevalence Among TB Cases, 2007

mate: about 1.4 million TB/HIV cases and 450,000 TB/HIV deat


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The HIV/AIDS Pandemic

UNAIDS and WHO estimate that in 2008:

33.4 million people living with HIV; 67%

in Sub-Saharan Africa

2.7 million new HIV infections worldwide

2 million AIDS-related deaths
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The HIV/AIDS Pandemic

HIV/AIDS is the worlds most deadly

infectious disease killing more than 25

million people since the disease was

first recognized in 1981

Despite years of research, there is stillno cure or vaccine for HIV/AIDS


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HIV/AIDS and TB:

A Deadly Combination

HIV suppresses the human immune system

TB suppresses the human immune system Each makes the other worse synergistically

The number of new cases of TB has more than doubled incountries with high HIV prevalence in the past 15 years

Onein

fou

rHIV

dea

ths

islinke

dto

TB

+
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TB/HIV Co-infection

TB is the leading cause of death PLWHA in Africa and amajor cause elsewhere

TB is the most common presenting illness among people

living with HIV on ARV treatment worldwide

1.4 million of the new TB cases in 2008 were in peopleliving with HIV; 78% in the African Region

500,000 people died of HIV associated TB in 2008

+


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TB Drug Resistance

WHO estimates 490,000 MDR-TB cases emerge everyyear, with more than 110,000 deaths

Extensively drug-resistant (XDR) TB has been identified in

57 countries as of November 2009

In 2008, WHO reported that the highest rates of MDR TBever recorded, with peaks of up to 22% of new TB cases,were in some settings of the former Soviet Union. In the

same region, 1 in 10 cases of MDR-TB is XDR-TB

Treatment for drug-resistant TB is much longer, morecomplex and more expensive - with much lower successrates


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TB/HIV A Human Rights Issue

No vaccine to provide long-term protection frompulmonary TB

No HIV vaccine

No benefit from biomedical advances for people andcommunities affected by TB

TB exposure due to inadequate health systems poordelivery of INH prophylaxis

TB and HIV diagnostics inadequate for testing children

Poor pediatric tracking programs to measure incidence

Social circumstances lead to exposure poverty,malnutrition


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Maternal TB/HIV important risk factor for

pediatric TB and mortality Estimated TB rate:

-10 times higher in HIV-exposeduninfected children


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Why do we need new tools for TB/HIV?

Diagnostics - More than 100 years old Particularly ineffective for diagnosing TB in people with

HIV/AIDS

Newer, more effective methods are not widely used Tests for drug-resistant strains not widely available in the field

Diagnostics suitable for community level still do not exist

Drugs - More than 40 years old Four drugs, taken for 6-9 months Not compatible with some HIV/AIDS antiretrovirals Treatment for resistant strains lengthy, expensive and toxic

with lower success rates

Vaccine - More than 85 years old Unreliable protection against pulmonary TB or past infancy Not safe for use in infants infected with HIV


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Barriers to Research & Development

of New Tools

Scientific uncertainty

Market uncertainty

Too much risk relative to perceived gain forprivate sector

Lack of clinical trial and manufacturing capacity


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Addressing Barriers through

Product Development Partnerships (PDPs) Non-profit enterprises created to accelerate R&D for new products to

fight AIDS, TB, malaria and other neglected diseases

Manage resources and partnerships from across public, private andphilanthropic sectors

Complements partners expertise, facilities and capacity

Utilize a portfolio management approach

Act as a catalyst to advance new products through the developmentpipeline towards registration and launch

Range from virtual to bricks and mortar depending on availabilityof external capacity

Commitment to access, availability and affordability


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New Tools: Target Product Profiles

Drugs: new affordable TB drugs that will dramatically

shorten treatment time, work against drug-resistant TB,

be compatible with HIV antiretrovirals and improve

treatment of latent TB. Diagnostics: rapid, accurate and affordable TB tests and

point-of-care diagnostics to more efficiently detect TB and

drug-resistant forms of TB.

Vaccines: new, safe, effective and affordable vaccine

regimens to protect against all forms of TB MDR and

XDR, to prevent TB in children, adolescents and adults,

and to be safe for use in people infected with HIV


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New Tools In the Pipeline

Available Now:

1st Wave of Innovation

Point of care diagnostic(detects resistance?Better for use in peoplewith HIV?)

New drug 4-month drugregimen which can beadministered with ARVsand is active againstdrug-resistant TB

Holy grail diagnostic

Significantly shorter (lessthan 2 months) TBregimen

New TB vaccine that willprevent all forms of TB inall age groups and will besafe for use in peoplewith HIV

New diagnostic availablefor peripheral lab settings{specify}

New diagnostic availablefor referral lab settings{specify}

2015 and beyond:3rd Wave of Innovation

2012 - 2015:2nd Wave of Innovation


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2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Dista

ncefrom

Patients

95%

Peripheral Lab

First Referral Level

70%

10-40%

%

Accessaf te

r5

years

Rapidculture&DST

Automa

tedNA

AT

(detect

ion&D

ST)

Manua

lNAAT

(DST)*

Improved

microscopy

Manu

alNAA

T

(detection

)

***

Predictive

LTBI

Rapid

speciation

POCtest

(detection)

Non-comm

ercial

cultureme

thods

Rapidc

olorime

tricDS

T

Community HealthCare

Manual

NAAT

(detec

tion)**

Abbreviations

DST: Drug Susceptibility TestNAAT: Nucleic AcidAmplification TestLTBI: Latent TB InfectionPOC: Point of Care

* Manual NAAT: technology for MTB Drug Susceptibility Testing (Line Probe As

* * Manual NAAT: technology for MTB detection at the Peripheral Lab* * * Manual NAAT: technology for MTB detection at the Community Health Care

Technologies in boxes: endorsed byWHO

Diagnostics Pipeline


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Partner Sites for TB Diagnostic Trials>50 trial sites in 25 countries

18 sites in Africa, 19 in Asia, 7 in Americas, 8 in Europe

Office in India and Uganda

MOUs with >17 MOH & NTP Strong partnerships with international agencies


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The Global Drug PortfolioTesting combination regimens with multiple new drugs

Bayer,

TB Alliance

Oflotub,

TDR

J&J/Tibotec

Otsuka

TB Alliance

Sequella

Lupin

Pfizer

Phase I Phase II Phase III


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TB Alliance Clinical Sites for New TB Drugs

Mexico

Peru

Kenya

Korea

Delhi

South Africa (5)

Taiwan

Hong Kong

Thailand (3)Malaysia

China (3)

Tanzania (2)

Zambia


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Global 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 ResearchInstitute; Institute de Pharamacologie, Puso; Karolinska Institute; Malaysia-Finlay Institute, NIAID; NIH; Osaka University; Shanghai H&G Biotech; Sequella; UCLA; and, Vanderbilt University.

AERAS402/Crucell Ad35

Crucell N.V./Aeras

MVA85A/AERAS-485OETC/Aeras

kingGroup

onNewTBVaccines


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Aeras Partnerships for Field Research

/UCT

,Sou

thAfrica

Makere r

eUniversity,U g

anda

KEMRI/CDC,Ke

nya

StJohn s

Researc

h

Institut e

,Ind

ia

C

ambod

ianHealth

Co

mmit

tee,Cambodia

anhica

Health

ResearchCen

tre

Mozambiqu

e


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Existing TB Vaccine Ineffective

BCG unreliable against pulmonary TB,which accounts for most TB diseaseworldwide

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

in1921


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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 worlds infants is

too risky to give to those born infected with the AIDS

virus, says a new study published by the World HealthOrganization. It recommended that vaccination be

delayed until babies can be tested.


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WHO 2007 Recommendations on BCG

Children with HIV infectionregardless of symptoms should notbe BCG vaccinated

All high risk infants need HIV

screening Maternal antibody masks antibody

tests Detection of virus required Very difficult to implement in many

places

HIV

infecte

dinfantsrec

ently(200

9)

estima

ted

00

(He

sseling,et

al )


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Goals for Better TB Vaccines

Eliminate TB as a public health

threat, in line with global targets

(


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Aeras Global TB Vaccine Foundation

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

Method

Collaborate with academic, biotech,pharmaceutical and NGO partners todevelop and test new TB vaccines

Purse a Prime-Boost strategy bydeveloping a modern replacement forBCG plus booster vaccines

Develop vaccines in its own lab andmanufacturing plant


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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

G


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Safer in HIV infected infants orothers with immune-suppression

BCG or rBCG boosted with another

TB vaccine is much better than

either vaccine alone Constructed to address each stage

of the TB life cycle

Prevent infection and reactivation

A new vaccine candidate with all of

these properties is expected to

enter clinical trials in 2010

R

ecomb in

antBCG

(rBCG


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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 are

encouraging for post-BCG prime-boost strategy

SSI HyVac4 / AERAS-404 Status: Phase IRecombinant 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+ in

EuropeAERAS-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 IIb

Viral 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


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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 health

care/research capacity to perform futureGood Clinical Practice (GCP) compliantPhase III clinical trials


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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 theinfrastructure 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


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Activities in South Africa - SATVI

Research Partner - South African Tuberculosis Vaccine

Initiative (SATVI)

Conducting Phase I, II and IIb studies offourvaccine

candidates

Adult and infant enrollment Over 230 staff trained since 2004

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

world

Future infant studies planned of AERAS-402/Crucell Ad35

Western Cape


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Activities in South Africa - UCT Lung Institute

Research Partner University of

Cape Town Lung Institute

Phase II clinical trial in adults with

active or previous TB (AERAS-402/Crucell Ad35 )

Cape Town

Future study of TB vaccine

candidate in HIV infected adults

planned (part of multi-centerMVA85A/AERAS-485 study)


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Activities in South Africa Aurum Institute

Research Partner Aurum Institute Enrolling adults with HIV in Phase IIb trial

Safety and efficacy of TB vaccine (MVA85A/AERAS-485)

Klerksdorp, North West (mining area)


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Key Accomplishments at Other Partner Sites

State-of-the-art immunology andmycobacteriology laboratory established inIndia

Mycobacterial lab capacity is being augmentedin Kenya and Uganda

Local staff trained in clinical research inKenya, Uganda and India

Epidemiological cohort studies in Cambodia,India,Kenya and Uganda

Quality management and data managementinfrastructure developed in India and Uganda

Vaccine trials being conducted in Kenya


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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


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Building Manufacturing Capacity

Reduce the cost and time tomanufacture and deliver vaccines to allwho need them

Produce enough bulk doses of vaccine

to meet the worlds estimated need Work with partners in countries such

as India, China, Korea and SouthAfrica to produce, fill, finish anddistribute vaccines at the lowest

possible price Ensure uniformity of quality

Minimize lag time between licensureand distribution


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Summary

New TB vaccines, drugs and diagnostics

will help achieve global development goals

are critical to controlling TB pandemic

will reduce the cost and burden of TB on patients, health caresystems and national economies

PDPs are leading the effort to develop new TB tools that will beaffordable and accessible worldwide, engaging stakeholders from acrosssectors toward common goals

Research collaborations in TB endemic countries build and strengthenresearch capacity, and are critical to advancing product candidates

New tools need to be a global priority to help ensure rapid developmentand distribution


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Aeras gratefully acknowledges the support of

the following major donors

NetherlandsMinistryofForeignAffairs

THE MARY LYNN

RICHARDSON

FUND

Documents

TB and HIV/AIDS (Peg Willingham)