Dr. Chia-Wei Tsai - Raxibacumab Experience
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Transcript of Dr. Chia-Wei Tsai - Raxibacumab Experience
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
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 4
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
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 5
BARDA MCMs under Project BioShield
Botulism
Anthrax
Smallpox
Chemical
Radiation
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 6
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
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 9
• 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
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 10
• 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
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 11
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.
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 12
• 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
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 13
• 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
14
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 15
Raxibacumab Field Study
ASPR: Resilient People. Healthy Communities. A Nation Prepared. 16
• 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: [email protected]• Upcoming Events• PHEMCE Strategy and Implementation Plan• CBRN and Pan Flu Programs • Business Toolkit
─ www.phe.gov/amcg
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