This is a presentation delivered by Dr. Chia-Wei Tsai, at the STFC Futures / RUSI Conference Series: Data for Security and Resilience 2014

1. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 0
United States Department of
Office 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 Officer
Antitoxins and Therapeutic Biologics Branch
BARDA/ASPR/HHS
March 7, 2014

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

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

4. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 3
Discovery Phase I Phase II LicensurePhase III
Preclinical
Development
Production
& Delivery
PROBABILITY OF SUCCESS TO LICENSURE
PRODUCTPIPELINEPRODUCTPIPELINE
Licensed
Product
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 III
Preclinical
Development
Production
& Delivery
PROBABILITY OF SUCCESS TO LICENSURE
PRODUCTPIPELINEPRODUCTPIPELINE
Licensed
Product
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 yrsTIME
$100M -130M $60-70M $70M-100M $130M-160M $190M-220M $18M-20M
PIPELINE
PHASE COST
Valley
of
Death
Pharmaceutical Product Development

5. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 4
BARDA MCMs
under Project BioShield
Botulism
Anthrax
Smallpox
Chemical
Radiation

6. ASPR: Resilient People. Healthy Communities. A Nation Prepared.
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 5

7. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 6
• 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

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

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

10. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 9
• 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

11. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 10
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.

12. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 11
• 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

13. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 12
• 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

14. 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
13

15. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 14
Raxibacumab Field Study

16. ASPR: Resilient People. Healthy Communities. A Nation Prepared. 15
• 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

17. ASPR: Resilient People. Healthy Communities. A Nation Prepared.
Contact Us
BARDA:
URL: http://www.phe.gov
BARDA e-mail: BARDA@hhs.gov
• Upcoming Events
• PHEMCE Strategy and Implementation Plan
• CBRN and Pan Flu Programs
• Business Toolkit
─ www.phe.gov/amcg
 Tech Watch program
 Federally-sponsored conferences
 Funding opportunities
 Resources 7 core service programs
 Regulatory guidance
 Federal strategies and reports