Tb Vaccines

Ann M. Ginsberg, MD, PhD

Aeras and the Global Effort to Develop New TB

Vaccines

J2J Workshop, Kuala Lumpur14 November 2012

DRIVING INNOVATION

Tuberculosis: A Devastating Epidemic

• Over 2 billion people or 1/3 of the world’s population is infected with M. tuberculosis

• Globally, 8.7 million new cases and 1.4 million deaths in 2011

• In SE Asia and Western Pacific, 5.2 million new cases and 610,000 deaths (excluding HIV) in 2011

• Globally, 13% of TB patients are HIV-infected.

• MDR-TB = 3.7% of new cases, globally. XDR-TB identified in 84 countries. Surveillance inadequate in many countries.

3

Number of MDR-TB cases estimated to occur among notified pulmonary TB cases,

2011

XDR-TB: approximately 9% of MDR-TB cases are extensively drug-resistant TB (XDR-TB). As of Oct. 2012, 84 countries had reported at least one XDR-TB case.

The energy and approaches we have put into addressing TB over the

past 20 years have led to insufficient progress.

6AERASDRIVING INNOVATION

Vaccines needed to turn the tide

Source: Christopher Dye, WHO

Global Plan will not eliminate TB by 2050

1

10

100

1000

10000

2000 2010 2020 2030 2040 2050

Year

TB

inc

ide

nc

e/m

illio

n/y

r

Elimination -16%/yr

Global Plan -6%/yr

Current trajectory -1%/yr

Projected incidence in 2050 >100x elimination

threshold

Current trajectory -1.6%/yr

Global Plan - 6%/yr

Elimination - 16%/yr

BCG – current TB vaccine• BCG developed 90 years ago,

not improved upon since.• Most widely delivered

vaccine in the world.• Reduces the risk of severe

pediatric TB disease, but:− Unreliable protection against

adult pulmonary TB, which accounts for most TB worldwide

− Not recommended for use in infants infected with HIV

− Many genotypes and phenotypes -- multiple BCGs

− Inadequate impact on the global TB epidemic

X

The Need for Improved TB Vaccines

(BCG)

The Potential of New TB Vaccines

New, more effective TB vaccines could:

• Be safer and more 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

• Play a crucial role in global efforts to control TB

Save lives

Break the cycle of transmission

Reduce cost burden to health systems

Increase productivity

A new vaccine

AERAS• Located in Rockville, Maryland, USA, Cape

Town, SA and Beijing, China• Nonprofit research organization operating as

a product development partnership • Mission:

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

• Fully integrated biotechnology organization

13

Regulatory Clearance

Preclinical Development

Discovery Process Development

cGMP Clinical

Manufacture

Clinical Trials Support

Aeras: a Product Development Partnership (PDP)

AERAS

FUNDERS

ACADEMICS

GOVERNMENTS

MANUFACTURERS

CLINICAL SITES

PHARMA/BIOTECH

Collaborating, catalyzing, conducting…

Strategies for TB Vaccine Development

• Pre-infection: to prevent initial or latent infection or disease− Improved priming vaccines− Novel booster vaccines− Infants; LTBI(-)s

Block Initial Infection

Prevent Early Disease

Prevent LatentInfection

Prevent Reactivation

Disease

• Post-infection: to prevent primary +/or reactivation disease

− Novel booster vaccines to extend and enhance immune protection

− LTBI(+) adolescents and adults

• Immunotherapeutic: to improve therapy − Shorten the course of chemotherapy

for active TB or latent TB infection− Improve efficacy of MDR/XDR/TDR-

TB treatment

Global Clinical TB Vaccine Pipeline – 2012

Ad5 Ag85AMcMaster CanSino

VPM 1002Max Planck, VPM,

TBVI

Hybrid-I + IC31SSI, TBVI, EDCTP,

Intercell

Phase II Phase IIIPhase IIbP h a s e I

Immunotherapeutic: Mycobacterial –

whole cell or extract

ID93 + GLA-SE IDRI, Aeras

Hyvac 4/ AERAS-404 + IC31

SSI, sanofi-pasteur, Aeras, Intercell

H56 + IC31SSI, Aeras, Intercell

MVA85A/AERAS-485

OETC, Aeras

AERAS-402/ Crucell Ad35Crucell, Aeras

RUTIArchivel Farma, S.L

Mw DBY, India, M/s.

Cadila

M. VaccaeAnhui Longcom,

China

M72 + AS01GSK, Aeras

MTBVACTBVI, Zaragoza,

Biofabri

rBCG

Viral vector

Protein/adjuvant

Attenuated M.tb

Our Approach


We work with partners to review and prioritize candidates with a goal of advancing at least two candidates to Phase III efficacy trials. With each advance, we collaborate to adjust site capacity, regimens, R&D, and regulatory approaches.

TB is complex and may require more than one vaccine to address geographic variations in the strains, stages of the disease, and populations. We continually invest in next-generation candidates, applying lessons learned and fostering novel partnerships and approaches.

In collaboration with partners, we evolve and standardize processes to focus on the most promising investigational vaccines. By using scientific approaches including challenge models, systems biology and innovative vaccine designs we accelerate advancement and cut costs.

We mobilize resources across public and private entities to sustain the growing costs of TB vaccine R&D efforts as we advance toward the finish line. Only by expanding our network of support and forging new partnerships can we address the immense scientific challenges and global need.


Vaccines that prevent adolescents and adults from TB would be the single greatest advance against the disease.

Vaccine – adol/adult

4.2M

There is tremendous momentum in clinical development. Aeras and its global partners are currently testing six candidates in clinical trials.

Aeras partners globally to conduct epidemiological studies and

clinical trials.

Clinical Studies


TB Vaccine Development:a decade of progress but much more to do

2000 202 2009 2011

2000 2002 2009 2012

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, 13 currently in clinical trials

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

• First human efficacy data expected early 2013 (MVA85A/AERAS-485); major milestone

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

• Substantial challenges remain; solutions will require global partnership and commitment.

• With sufficient resources and positive results from current clinical trials, the first new TB vaccine could be approved within a decade.

Identifying five keys to progress

• Creativity in research and discovery

• Correlates of immunity and biomarkers for TB

vaccines

• Clinical trials – harmonization and cooperation

• Rational selection of TB vaccine candidates

• Building support through advocacy

communications,

and resource mobilization

The TB Vaccine Blueprint


Keys to Progress

Aeras serves as a catalyst by investing in the world’s most promisingTB vaccine candidates and coordinating a diverse community of global scientists, researchers, governments, and funders on a single mission:the development of effectiveTB vaccines.

Collaboration is key in an unprecedented effort


Funding and collaboration needed to advance global TB vaccine efforts


The next phase of new vaccine development is the most critical—

and requires that the global community significantly scale efforts .

This cannot be the work of a single foundation or a small set of

government or biotech partners, but of a much larger global

community.

$78M

2010 global TB vaccine funding

Global Plan annual target

$380M

from TAG Report 2011

Major Contributors


Aeras Gratefully Acknowledges the Volunteers in Our Clinical Trials, Hard Work of Many Partners including Clinical Trial Sites, and Support of these Major Contributors

Thank You!For more information:

[email protected]

Hello, my name is Mycobacterium tuberculosis! I am the king of the pathogens, killing more people than any other infectious agent except HIVFrom: http://ilovebacteria.com/

Tb Vaccines

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