The Evolving 'Polio Endgame' Strategy Orientation for IEAG 15 March 2012

Background

Main risks if routine OPV is continued after wild poliovirus eradication Cases of Vaccine-Associated Paralytic Poliomyelitis (VAPP): very rare severe adverse event, occurring in OPV recipients or a close contact. Outbreaks of circulating vaccine-derived poliovirus (cVDPV): very rare event; > 1 paralytic polio case with isolation of related but non-identical VDPV viruses.

Other risk: long-term poliovirus excretors (iVDPVs: 1o immunodeficiency-associated VDPVs) 53 iVDPVs (> 6 months excretion) 8 known to excrete >5 years. Type 2 (34) > Type 1 > Type 3 From: Industrialized countries (22) Middle income countries (31) Low income countries

'After interruption of wild poliovirus, continued use of OPV would compromise the goal of a polio-free world. Expert Consultation on Vaccine-derived Polioviruses (VDPVs), Sept 2003, Geneva

Evolution of the 'Post-Eradication' Timeline Last WPV case OPV cessation Years 0 2 4 6 8 10 12 Wild virus eradication Global Cert Comm (1995) Certification The 'Polio Endgame' refers to management of the 'post-eradication' risks due to OPV. Expert Advisory Meeting (1998) Wild virus eradication Certification & containment ACPE (2004) VDPV elimination? Wild virus eradication Certification & containment VDPV elimination & validation World Health Assembly (2008) Post-OPV surveillance

Why is the world now rethinking the Polio Endgame?

Recent developments allow a major 'rethink' of the polio endgame New diagnostics and experience currently suggest type 2 cVDPV is the main 'post-eradication' problem. New bivalent vaccine (bOPV) is proven to outperform tOPV for types 1 & 3 and a viable option to replace tOPV. New, very low cost 'IPV options' could allow all countries to continue type 2 immunization if they want/need to.

Current Understanding of cVDPVs (Global) Circulating Vaccine-Derived Poliovirus Oubreaks (cVDPVs) 2000-2010 Type 1 (79 cases) Type 2 (450 cases) Type 3 (9 cases) Since 2009, 97% of cVDPV cases are due to type 2 (& 40% of VAPP)

Current Understanding of cVDPVs (India) Spot map of VDPVs 2011-12 India: 90% of VDPVs are type 2 & 100% of cVDPVs are type 2 Year Type 1 Type 2 Type 3 Total a i c 2009 1 4 15 21 2010 2 5 2011 7 2012  1   10 3 17 34 Data as on 7 March 2012 10

Trend in Type 2 Polio Protection (India) Moradabad Nov 2007 (N=121) AFP cases UP Nov 08 – mid 09 (N =169) Moradabad May 2009 (N=534) UP & Bihar Aug 2010 (N=1280) Aug 2011 (N=1246) Age 6-7 mos 6-11 mos Type 2 56% 33.7% 75% 65% 85% Reduced emergence of type 2 cVDPVs is associated with improving type 2 immunity

Bivalent OPV Efficacy & Use Seroconversion after 2 x bOPV vs. tOPV, India, 2008-2009 bivalent OPV use as of Sept 2011 Introduced Dec 09-Aug 11 Planned by end-2011 Type 1 Type 3

Affordable IPV options in the short-term, 1/5th of 1 dose of IPV can induce a response in >90% of children Response* after 1 dose (%, intradermal IPV, Cuba) * includes seroconversion & priming Full-dose $3 $0.6 Current price (low volume) < $0.3 IPV price ($ per dose) ** assumes full dose price of < US$1.5/dose at high volume 1/5th of 1 dose of IPV could be very affordable (<$0.5/dose) 1/5th fractional dose Expected price (high volume**)

What are the major elements of the 'New Polio Endgame'?

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 at least 1 dose of IPV to boost immunity prior to a tOPV-bOPV switch (& provide type 2 priming if further doses required).

A new 'Endgame' strategy: parallel instead of sequential risk management Last wild polio case trivalent OPV cessation Years 0 2 4 6 8 10 12 Sequential risk management Wild virus eradication Certification & containment VDPV elimination & validation Post-OPV surveillance Wild virus eradication Parallel risk management Certification & containment VDPV2 elimination & validation Post-OPV surveillance OPV2 cessation & IPV introduction bivalent OPV 1&3 (bOPV) cessation

Potential Advantages of the New Approach accelerate eradication of type 1 & 3 wild poliovirus by routine use of bOPV (and possibly IPV) address >90% of the VDPV risk when global surveillance/response capacity is highest substantially shorten the post-eradication phase (& reduce a major source of donor/partner anxiety) possibly boost eradication effort with new energy & routine immunization coverage (i.e. if IPV dose at DPT3)

Potential Disadvantages of the New Approach distraction to wild poliovirus eradication efforts (to stop ongoing cVDPV2s; to coordinate tOPV-bOPV switch). complications of adding a new vaccine (IPV) (however, GPEI has introduced many new vaccines already). sudden 'price shock' for donors as requires early presentation of longer-term financing requirements. risk of failure to stop new cVDPV2s (but, with this approach could even 'restart' tOPV temporarily if needed).

Impact of the new Endgame Strategy on Major Cost Drivers for 2013-2018 'Core costs*' - stable OPV campaign costs - decrease IPV costs - additional * staff & technical assistance, surveillance & lab, research, outbreak response, stockpiles.

Some Implications for IPV IPV could be scaled up much earlier than anticipated (i.e. tOPV-bOPV switch could be prior to April 2014). standalone IPV would be used for the 'tOPV-bOPV switch' with hexavalent having a 'post-OPV' role (e.g. from 2017-18). a fractional (1/5th dose) intradermal IPV option may be essential for acceptability, cost, supply, manufacturer risk. the probability of expanded, longterm IPV use would increase substantially.

Recent Developments & Next Steps

SAGE Nov 2011: recommended endgame strategy be based on phased, not simultaneous, Sabin strain removal. WHO Executive Board Jan 2012: requested endgame strategy & timeline for phased Sabin strain removal. SAGE Apr 2012: to discuss introduction of 1 dose of IPV at DTP3 contact in all OPV-using countries at least 6 months prior to a global tOPV-bOPV switch (as early as Apr 2014). World Health Assembly, May 2012: to consider a resolution on the tOPV-bOPV switch.

Summary a new definition of, and strategy for, the 'endgame' may accelerate eradication & reduce long-term risks. depending on IPV price and strategy, the new endgame could be cost-neutral through certification. by emphasizing the delivery of 1 IPV dose at the DPT3 contact, the new strategy should help to strengthen the focus & coverage of routine immunization.

Extra Slides

Major Issues (examples) Work streams Major Issues (examples) Phased vs. simultaneous removal of Sabin viruses Geographic extent and schedule for IPV use Policy development Global bOPV availability (i.e. national producers) Feasibility of restarting tOPV production from bOPV Regulatory issues, supply & price for largescale ID IPV use Supply & Product Development Nature of immune response & duration of priming after 1 IPV dose Further characterization of VDPV risks Research Criteria to validate WPV type 2 elimination; cVDPV2 elimination Containment requirements for type 2 after tOPV-bOPV switch Supplementary surveillance (incl. environmental surveillance) Surveillance & containment Operations & logistics Synchronization of tOPV-bOPV switch globally Safe handling/destruction of residual stocks Budget & financing Budget implication of IPV introduction Multi-year business & financing plan 25