ASPR: Resilient People. Healthy Communities. A Nation Prepared. 1

United States Department of

Health & Human ServicesOffice of the Assistant Secretary for Preparedness and Response

Raxibacumab Experience:The first novel product approved under

the FDA’s “animal rule”

Dr. Chia-Wei Tsai, Project OfficerAntitoxins and Therapeutic Biologics Branch

BARDA/ASPR/HHS

March 7, 2014

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 2

• USG strategy on Anthrax─ What is BARDA?─ Anthrax as the threat

• Raxibacumab experience─ The road to licensure under the Animal Rule─ Lessons during the Approval─ Post licensure commitment

Overview

ASPR: Resilient People. Healthy Communities. A Nation Prepared.

3

BARDA’s Commitment to Medical Countermeasures

Mission:

Develop and provide countermeasures for CBRN threats, pandemic influenza, and emerging infectious diseases by product development, stockpile acquisition, building manufacturing infrastructure, & product innovation.

Your Anthrax Team

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Discovery Phase I Phase II LicensurePhase IIIPreclinical

DevelopmentProduction & Delivery

PROBABILITY OF SUCCESS TO LICENSURE

PR

OD

UC

T P

IPE

LIN

EP

RO

DU

CT

PIP

EL

INE

LicensedProduct

1-3% 5-17% 10-25% 18-35% 45-70% 90%

IND NDA/BLA

PHASESPHASES

NIH ($11.8B)

BARDA ($540M)

Project BioShield ($5.6B)

Discovery Phase I Phase II LicensurePhase IIIPreclinical

DevelopmentProduction & Delivery

PROBABILITY OF SUCCESS TO LICENSURE

PR

OD

UC

T P

IPE

LIN

EP

RO

DU

CT

PIP

EL

INE

LicensedProduct

1-3% 5-17% 10-25% 18-35% 45-70% 90%

IND NDA/BLA

PHASESPHASES

NIH ($11.8B)

BARDA ($540M)

Project BioShield ($5.6B)

BARDA ($2.0 B)

NIH ($15.6 B)

3-7 yr 0.5-2 yr 1-2 yr 2-3.5 yr 2.5 -4 yr 1-2 yrs TIME

$100M -130M $60-70M $70M-100M $130M-160M $190M-220M $18M-20MPIPELINEPHASE COST

Valley of

Death

Pharmaceutical Product Development

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BARDA MCMs under Project BioShield

Botulism

Anthrax

Smallpox

Chemical

Radiation

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Anthrax Threat

• Category A Threat Agent─ Poses greatest possible threat to public health,

economic, social and political disruption─ May spread across large areas─ Environmental decontamination difficult─ Great deal of planning needed to protect public─ Documented BW agent in former offensive programs

• Amerithrax case in 2001─ Seven letters mailed over two weeks

• 11 cases of inhalational anthrax developed

• 5 resulted in death

─ Material Threat Determination (MTD) published by Dept of Homeland Security in 2004 to support Project BioShield

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 7

• USG strategy on Anthrax─ What is BARDA─ Anthrax as the threat

• Raxibacumab experience─ The road to licensure under Animal Rule─ Lessons during the Approval─ Post licensure commitment

Overview

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 8

Anthrax Antitoxin

Raxibacumab • manufactured by Human Genome Sciences, Inc. (HGS, acquired by GSK in

2012) • a humanized monoclonal antibody that binds to the Protective Antigen of

Bacillus anthracis

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• Animal models used to provide efficacy data• Human trials used for safety data• For therapeutics

─ Larger efficacy database, smaller safety database

• For vaccines─ Smaller efficacy database, larger safety database

• Animal Rule is not a shortcut to licensure or approval─ Development of animal model and correlates or surrogates

not straightforward

FDA Animal Rule

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• Product Information ─ Indication:

• For the treatment of adult and pediatric patients with inhalational anthrax in combination with appropriate antibacterial drugs

• For prophylaxis of inhalational anthrax when alternative therapies are not available or not appropriate.

• Product availability─ ~ 65,000 treatment courses delivered and available in SNS─ Storage: 2-8°C─ Shelf life: 5 years─ Approved on Dec 14, 2012─ Approval under the FDA Animal Rule

Raxibacumab

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Post-Marketing Commitments

• Field Study─ Conduct a field study to evaluate the efficacy, pharmacokinetics,

and safety of raxibacumab use for Bacillus anthracis in the United States.

• Vaccine Interaction─ Conduct a Phase 4 study to evaluate the effect of raxibacumab

on immunogenicity of anthrax vaccine.• This is to support used for PEP

• Manufacturing Controls─ Perform spiking studies of BDS to evaluate whether endotoxin

masking occurs over time in undiluted samples.─ Develop and validate a new host cell protein assay.

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• Where?─ Unknown location provides challenge for IRB approval─ Logistics to communicate with CDC for raxibacumab

distribution

• Who?─ Training for the data collection─ Sample handling and transportation

• When?─ Need to maintain solutions for where and who until needed

Challenges for Field study

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• Final Study Protocol approved by FDA

• CDC has a bridging protocol which is to be transitioned to our GSK protocol once all set-up activities are complete (from April 2014)

• Next steps: ─ CRF, Database set-up, identifying potential ref sites, site

training/study awareness and mechanism for expedited IRB approval, site contracts and site initiation

─ Communication plan with CDC for trigger for site initiation─ Data monitoring plan (including in-stream monitoring of

safety data)

Raxibacumab Field Study Status

ASPR: Resilient People. Healthy Communities. A Nation Prepared.

Raxibacumab Field Study:Protocol Overview

A phase IV, open-label study to evaluate the clinical benefit, safety and pharmacokinetics in subjects treated with raxibacumab following exposure to Bacillus anthracis

• First human study to collect data on B. anthracis-infected or exposed patients treated with raxibacumab

• First study to gain a better understanding of the clinical benefit and safety of raxibacumab in human subjects

• Data from this study will further inform patient care and treatment choices for management of anthrax

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Raxibacumab Field Study

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• Product versus policy─ Development of policies must keep pace with development

of products─ Operational concepts, clinical guidance, prioritization

• Commitment to long-tern strategy required, requirements will change

• When are we done?─ Ultimate objective must be identified─ Complete lifecycle must be considered

Lesson learned

ASPR: Resilient People. Healthy Communities. A Nation Prepared.

Contact Us

BARDA:URL: http://www.phe.govBARDA e-mail: BARDA@hhs.gov• Upcoming Events• PHEMCE Strategy and Implementation Plan• CBRN and Pan Flu Programs • Business Toolkit

─ www.phe.gov/amcg

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