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The Evolving 'Polio Endgame' Strategy

Orientation for IEAG

15 March 2012

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Background

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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.

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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

Immunodeficiencies linked to prolonged poliovirus excretion

cvid

agamma

ab deficient

scid

hypogamma

ICF

MHC-II def

XLA

unknown

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'After interruption of wild poliovirus, continued use of OPV would compromise the goal of a

polio-free world.Expert Consultation on Vaccine-derivedPolioviruses (VDPVs), Sept 2003, Geneva

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Evolution of the 'Post-Eradication' Timeline

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.

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Why is the world now rethinkingthe Polio Endgame?

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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.

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Current Understanding of cVDPVs (Global)

Circulating Vaccine-Derived Poliovirus Oubreaks (cVDPVs) 2000-2010

Since 2009, 97% of cVDPV cases are due

to type 2

(& 40% of VAPP)

Type 2 (450 cases)

Type 1 (79 cases)

Type 3 (9 cases)

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Spot map of VDPVs 2011-12

Data as on 7 March 2012

YearType 1 Type 2 Type 3

Totala i c a i c a i c

2009 1 1 0 4 0 15 0 0 0 21

2010 0 0 0 2 1 2 0 0 0 5

2011 0 0 0 4 2 0 0 1 0 7

2012  1                 1

Total 2 1 0 10 3 17 0 1 0 34

India: 90% of VDPVs are type 2 & 100% of

cVDPVs are type 2

Current Understanding of cVDPVs (India)

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Trend in Type 2 Polio Protection (India)

Moradabad Nov 2007(N=121)

AFP cases UPNov 08 – mid 09 (N =169)

Moradabad May 2009(N=534)

UP & BiharAug 2010(N=1280)

UP & BiharAug 2011(N=1246)

Age 6-7 mos 6-11 mos 6-7 mos 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

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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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Affordable IPV options in the short-term,

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**)

1/5th of 1 dose of IPV can induce a response in >90% of children

0

10

20

30

40

50

60

70

80

90

100

P1 P2 P3

Response* after 1 dose

(%, intradermal IPV, Cuba)

* includes seroconversion & priming

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

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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).

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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

OPV2 cessation& IPV introduction

bivalent OPV 1&3 (bOPV) cessation

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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)

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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).

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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.

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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.

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Recent Developments & Next Steps

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• 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.

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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.

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Extra Slides

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Work streams Major Issues (examples)

• Phased vs. simultaneous removal of Sabin viruses

• Geographic extent and schedule for IPV use

Supply & Product Development

Surveillance & containment

Operations & logistics

• Global bOPV availability (i.e. national producers)

• Feasibility of restarting tOPV production from bOPV

• Regulatory issues, supply & price for largescale ID IPV use

• Nature of immune response & duration of priming after 1 IPV dose

• Further characterization of VDPV risks

• Criteria to validate WPV type 2 elimination; cVDPV2 elimination

• Containment requirements for type 2 after tOPV-bOPV switch

• Supplementary surveillance (incl. environmental surveillance)

• Synchronization of tOPV-bOPV switch globally

• Safe handling/destruction of residual stocks

Budget & financing

• Budget implication of IPV introduction

• Multi-year business & financing plan

Research

Policy development