mopv & bopv: Licensing, Clinical Trials, and Strategies Manufacturer's Meeting, Geneva, 30 October 2008

Transcription

1 mopv & bopv: Licensing, Clinical Trials, and Strategies Manufacturer's Meeting, Geneva, 30 October 2008 Research and Product Development Team, Polio Eradication Initiative, WHO, Geneva

2 Focus of GPEI Research & Product Development To accelerate eradication. To provide the scientific base, and develop the necessary products, to make policy decisions and implement the post-eradication strategies.

3 Presentation Overview Background WHO Commitment Development of mopvs Licensure Clinical trials Use Status of bivalent OPV development Conclusions

4 Background mopv1 In September 2004 Ad-hoc Advisory Committee on Polio Eradication (ACPE) recommended development of mopv1 Initial development in France (sanofi pasteur & AFSAAPS) licensure in March 2005 (and India (Panacea Biotec Ltd licensure in December 2004) ACPE defined policy guidance for mopv1 use First uses in April 2005 in India and May 2005 in Egypt Followed by mopv3 (and mopv2) licensure

5 Policy Guidance for mopvs Use mopv1 only recommended for campaign use mopv1 not substitute for topv in routine programs With licensure of mopv3, program had to make sometimes difficult decisions which vaccine to use to optimize immunity More recently, use of short-interval rounds (~2 weeks) in difficult-to-access areas (Somalia & Afghanistan)

6 WHO Commitment for mopv1 Guarantee minimum purchase (50 million doses of mopv1) Prepare of key documents (clinical historical data, and expert report) Conduct clinical trials for WHOprequalification Assist with discussions with national regulatory agencies

7 mopv Licensure Producer Product Original licensure Licensure elsewhere Sanofi-Pasteur mopv1 France Egypt, Pakistan Panacea mopv1 India Nigeria, Pakistan*, Indonesia+ mopv3 India Nigeria, Pakistan* mopv2 India GSK mopv1 Belgium Egypt, Nigeria, Pakistan, India, Indonesia+ mopv3 Belgium Nigeria, Pakistan, India mopv2 Pending Novartis mopv1 Italy Nigeria, Pakistan, India mopv3 Italy Pakistan, India Bio Farma mopv1 Indonesia Nigeria Haffkine mopv1 India *in process; +special access scheme

8 Clinical Trials of mopvs Evaluate standard potency (same as in topv) for WHO-prequalification: mopv1&, mopv2, mopv3 Optimize formulation of mopv1: Evaluate higher-potency (10^6.8 CCID50) with regular-potency mopv1 (10^6.15 CCID50) in India Evaluate bivalent (1&3) OPV: Added to evaluation of mopv2 and mopv3 &N Engl J Med 2008;359:

9 Overview of Clinical Trials Country Vaccine/arms Status Main findings Egypt mopv1 sp / 2 arms Completed Superiority of mopv1 India1 mopv1 Panacea / 3 arms Completed Negative for birth dose India2 high-titer mopv1 Panacea/ 4 arms Completed Negative for birth dose /positive for 1-mos dose India3 bopv Panacea/ 5 arms (mopv1, 2, + 3) Field work in progress NA India4 Fractional IPV / mop1 (4 arms) Planned NA South Africa mopv1 + 3 / 4arms (GSK) Field work in progress NA Cuba1 Fractional IPV / 2 arms (SSI) 6,10,14 w Completed Inferiority of fractional dose Cuba2 Fractional IPV / 2 arms at 4&8 mos Planned NA Oman Fractional IPV GSK/ 2 arms 2,4,6 mos Almost completed Equivalency of fractional dose

10 mopv1 vs topv Seroconversion After a Dose Given at Birth mopv1 topv P values India % 10.2% NS India % 11.2% NS Egypt& 55.4% 32.1% <0.001 &N Engl J Med 2008;359:

11 mopv1 vs topv Seroconversion After a Dose Given at 1 Month of Age mopv1 topv P values India 1 ND ND NS India % 57.9% <0.001 Egypt& 58.3% ND NS &N Engl J Med 2008;359:

12 Two-Dose Cumulative Seroconversion of mopv1 vs topv At Birth & 1 Month mopv1 topv P values India 1 ND ND NA India % 62.6% <0.001 Egypt& 81.4% ND NA &N Engl J Med 2008;359:

13 Global mopvs Use, 2005-Present Year 2005 mopv1 (million) mopv3 (million) , ,216.8* 368.0* *2008 as of to date

14 Supplementary Immunization Activities, by Vaccine Type, Endemic Regions, 2008 Countries using mopv1 NID (12 countries*) SNID (7 countries) * a mix of mopv1 and mopv3 used in Nepal a mix of mopv1, mopv3 and topv used in Pakistan a mix of mopv1 and topv used in Afghanistan, Chad, India and Sudan Countries using mopv3 NID (5 countries*) SNID (2 countries**) * a mix of mopv1 and mopv3 used in Nepal a mix of mopv1 mopv3 and topv used in Pakistan ** a mix of mopv1 and mopv3 used in India Countries using topv NID (16 countries*) SNID (11 countries) * a mix of mopv1, mopv3 and topv used in Pakistan a mix of mopv1 and topv used in Afghanistan, Chad, India and Sudan Source: data in WHO/HQ as of 28 Oct 08

15 Bivalent (1&3) OPV Development Background All 4 polio-endemic countries have type 1 and 3 co-circulation Making programmatic decisions on which mopvs to use sometimes difficult Recommendation The ACPE recommended during November 2007 meeting that a bopv arm be added to an already planned clinical trial in India

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17 bopv Trial Design Objective: To determine whether bopv may provide similar immunity gains as do mopv1 and mopv3 administered individually bopv formulation: Identical to topv (except no Sabin 2 strain) Design: 5-arm study, bopv, mopv1, mopv2, mopv3 and topv Two doses administered at birth and 30 days, and blood collected at birth (cord blood), days Timeline: Field work expected to be finished by end 2008; preliminary results expected at end of 1 st quarter 09

18 Possible Trial Outcome I Scenario 1 bopv performs satisfactorily& (no decreases in type 1 seroconversion) Seek licensure of bopv in India Invite other WHO manufacturers to seek licensure in country of production and use Issue tender Scenario 2 bopv performs intermediately (small decreases in type 1 seroconversion) Decide to whether a formulation trial is needed to determine the optimal ratio & potency of type 1 and 3 Sabin strains &Please note: bopv should be as immunogenic as mopv1 for type 1; and as immunogenic as topv for type 3.

19 Possible Trial Outcome II Scenario 3 bopv performs unsatisfactorily& (large decreases in type 1 seroconversion) Abandon development efforts for bopv vaccine &Please note: bopv >20% less immunogenic as mopv1 for type 1; and as immunogenic as topv for type 3 or lower.

20 bopv Final Thoughts Clinical trial results will guide next steps Risk/benefit for bopv has changed since evaluation in 2000 (Parkman) Risk of VDPV emergence following bopv use needs to be assessed Reversion / recombination Risk management plan Designated staff for post-marketing surveillance

21 Conclusions Unprecedented collaboration for development & licensure of mopv1, mopv3, and more recently mopv2 (manufacturers & regulatory agencies) Evaluated product refinement in mopv1 (i.e., higher-potency mopv1) Unprecedented use of mopv1 and mopv3 in campaigns for polio eradication Evaluation for possible innovation continue with clinical trial of bopv to make best tools available to polio eradication