the challenge: how to accelerate eradication and the 'endgame'?
TRANSCRIPT
The Challenge: How to Accelerate Eradication and the
'Endgame'?
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Historical Evolution of 'Post-Eradication'
0 2 4 6 8 10 12
Years
Wild virus eradication
Global Cert Comm (1995)
Certification
Expert Advisory Meeting (1998)
Certification & containment
Wild virus eradication
Last WPV case OPV cessation
ACPE (2004)VDPV elimination?Wild virus
eradicationCertification & containment
VDPV elimination & validation
Wild virus eradication
World Health Assembly (2008)
Post-OPV surveillance
Certification & containment
The 'Polio Endgame' refers to management of the
'post-eradication' risks due to OPV.
VDPV: Vaccine-derived poliovirus ACPE: Advisory Committee for Polio Eradication
3
New polio endgame: Guiding principles
• phased removal of Sabin viruses, beginning with highest-risk (type 2).
• elimination of VDPV type 2 in parallel with eradication of last wild polioviruses by switching from tOPV to bOPV for routine EPI & campaigns.
• early introduction of IPV, at least in high risk areas for VDPVs, to provide type 2 protection.
4
A new 'Endgame' strategy: parallel instead of sequential risk management
0 2 4 6 8 10 12
Years
Last wild polio case trivalent OPV cessation
VDPV elimination & validation
Wild virus eradication
Sequential risk management
Post-OPV surveillance
Certification & containment
VDPV2 elimination & validation
Post-OPV surveillance
Wild virus eradication
Parallel risk management
Certification & containment
earlier IPV introduction &OPV2 cessation
bivalent OPV 1&3 (bOPV) cessation
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Implications
• First: Early universal IPV introduction (priority highest cVDPV risk areas) integrated into routine immunization program (before switch).
• Second: Switch from tOPV to bOPV in a globally synchronized manner. Switch date as early as April 2013.
• Third: For outbreak control, use IPV, mOPV2, or exercise re-start tOPV option
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Product development needs
• REQUIRED: Licensure of bOPV in all self-producing countries.
• REQUIRED: Appropriate presentations and labelling change to permit use of fractional-dose IPV (1/5 of full dose).
• OPTIONAL: Availability of appropriate jet injectors for intradermal administration.
Expanded Use of bOPV
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Bivalent OPV efficacy & use
79.5
53.2
71
49.1
0
10
20
30
40
50
60
70
80
90
100
bOPV tOPV bOPV tOPV
Seroconversion after 2 x bOPV vs. tOPV, India, 2008-2009
Type 1 Type 3
bivalent OPV use as of Sept 2011
Introduced Dec 09-Aug 11
Planned by end-2011
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Urgent bOPV priorities
• Licensure of bOPV in self-producing countries: Brazil, China, Iran, Mexico, Russian Federation, Serbia, Vietnam, ... .
• Regulatory approach: Reproduce licensing strategy that led to approval of six manufacturers.
• Label-change of current bOPV: Current bOPV licensed only for supplemental doses, not for primary immunization.
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bOPV data needs
• Clinical trial: bOPV administered in four-dose schedule ('EPI schedule'), with doses administered at 0, 6, 10, and 14 weeks.
• Modelling: Risk of cVDPV2 emergence, assessment of risk mitigation strategies.
• Mucosal immunity: Will bOPV induce type 2 mucosal immunity after IPV.
Fractional-dose IPV
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 2010. All rights reserved
Standalone IPV
IPV - hexa combo
Data in WHO HQ as of Sep 2010
IPV - penta combo
Unknown
Not applicable
Background: Countries with IPV Use
Affordable IPV Strategy: Approaches
• Enables IPV production in developing countries
with less or non-infectious strain
• Use adjuvant to reduce antigen contents per
dose
• Develop intradermal (ID) device or micro-
needle patch to stretch doses
• Use fewer doses per schedule Reduce number of doses
Reduce amount of dose
Reduce antigen content
Reduce production cost
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IPV priorities
• Product required: one- or two dose IPV presentation.
• Regulatory approval: label-change to include intradermal administration.
• Policy decisions: (1) fractional-dose IPV as supplemental dose(s) to current OPV schedule in routine immunization programs (either with DTP3 at 16 wks or with measles at 9 mos); and (2) fractional-dose IPV in supplemental immunization campaigns (SIAs).
Feasibility of Approach: Oman, GSK IPV at 2, 4, and 6 mos, Biojector2000®
ID n=187
IM n=186
P values
Poliovirus type 1 seroconversion, % [median titer]‡
97.3%
228
100%
724
NS
<0.001Poliovirus type 2 seroconversion, % [median titer]‡
95.7%
287
100%
1149
0.01
<0.001Poliovirus type 3 seroconversion, % [median titer]‡
97.9%
362
100%
>1448
NS
<0.001
Mohammed AJ, et al. N Engl J Med 2010;362:2351-9.
Single-dose Immunogenicity: Cuba, NVI IPV at 4 (and 8) mos, Biojector2000®
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
ID IM ID IM ID IM
1st dose Priming 2nd dose Not immune
P1 P2 P3 Randomized controlled trial Field work in Camaguey Province, Cuba IPV from Netherlands Vaccine Institute Enrolling 160 infants per arm Serum at 4m, 8m, 8m+7d and 8m+30d IPV at 4- and 8 m fractional vs full-dose Seroconversion (single and two-dose) Priming (8m and 8m+7d)
Preliminary Results Study design
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IPV data needs
• Clinical trial: non-inferiority of a fractional versus full-dose IPV (given with pentavalent vaccine at 14 wks and/or with measles vaccine at 9 mos)
• co-administration assessment (immunogenicity of different antigens, including hepatitis B)
• large scale-safety assessment • Immunology: Assessment of priming (difference from
seroconversion); duration of effect• Modelling: Geographic phasing, number of doses, full
versus factional dose IPV, outbreak control options
Intradermal needle-free devices
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Needle-free device priorities
• Product(s) required: intradermal device appropriate for developing countries (i.e., spring-powered).
• Regulatory approval: WHO-prequalification.
• Policy decision: use device to administer fractional-dose IPV in supplemental immunization campaigns (SIAs).
New Needle-free Intradermal-only Devices
Pharmajet
Bioject
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Device data needs
• Comparative evaluation: assessment of appropriate intradermal devices– immunogenicity, reactogenicity, ergonomics [planned in Cuba in 2012].
• Clinical trial: non-inferiority study of supplemental full-dose (by needle & syringe) or fractional-dose IPV (by needle-free device and needle & syringe) [planned in India for 2012].
22
Upcoming Consultations on new Endgame Strategy
• Spearheading partners+ (19 October)
• Polio Donor Contact Group (20 October)
• OPV/IPV Manufacturers (27 October)
• WHO's Scientific Advisory Body of Experts (SAGE) (10 Nov)
• Expert Consultation on VDPVs (January/February 2012)
• WHA Executive Board (January 2012)
• World Health Assembly (May 2012)
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Summary
• a new definition of, and strategy for, the 'endgame' could accelerate eradication & reduce long-term risks.
• depending on IPV price and strategy, the new endgame could be cost-neutral through certification.
• a number of workstreams would be needed to address major unresolved questions/risks (policy, R&D, vaccine supply, surveillance/validation, operations, financing).