1. Can we achieve rotavirus vaccine immunization worldwide by 202X? Global Vaccines 202X: Access, Equity, Ethics May 3, 2011

2. Topics Burden of illness Current use of rotavirus vaccines (public sector) Impact of rotavirus vaccines Intussusception Current pricing GAVI shortfall New rotavirus vaccines Challenges - new vaccine development Solutions? 2

3. Global burden of rotavirus Source: WHO. WER. 2009;84(51/52). 3

4. Status of rotavirus vaccine use (public sector) Source: WHO NUVI 24 countries have introduced vaccine to-date Birth cohort = 14 million 4

5. Nicaragua: effectiveness by severity (full course of vaccine) SeverityCommunity Controls Hospital Controls Mild to moderate (0-10) [33%] 23% (-74, 66)4% (-120, 38) Severe (>=11) [67%] 52% (18, 72)63% (34, 80) Very severe (>=15) [19%] 73% (18, 91)86% (46, 96) Patel, et al. JAMA. 2009; 309(21). Slide courtesy of K. Neuzil, PATH 5

6. Mexico: Impact on total diarrhea deaths after vaccine introduction Richardson et al. NEJM. 2010; 362(4). Diarrhea deaths among children <5, July 2002-May 2009 6

7. If we get vaccines where they are needed most… Global impact: 2.4 million lives saved (2007-2025) 1 Greatest impact in countries with highest burden Potential herd immunity: In El Salvador, ~41-68% decline in rotavirus hospitalization among children too old to be vaccinated. 2 1 Atherly, et al. JID. 20098; 200(S1) 2 Yen, et al. PIDJ. 2011;30(S1) 7

8. Efficacy estimates of current rotavirus vaccines generally correlate with mortality quartiles WHO mortality strata Under-5 child mortality Vaccine efficacyCountries HIGH Highest (top 25%) 50-64% Ghana, Kenya, Malawi, Mali INTER- MEDIATE LOW High mid (next 25%) 46-72% Bangladesh, South Africa Low mid (next 25%) 72 - 85% Vietnam, Region of the Americas Least (lowest 25%) 85 – 100% Region of the Americas, Europe, Western Pacific http://www.who.int/whosis/en/ WHO. WER. 2009. 84(51/52). Slide courtesy of K. Neuzil, PATH 8

9. Intussusception Rotashield: 1998, first rotavirus vaccine in the US. Voluntarily withdrawn from the market in October 1999, estimated to cause intussusception in 1 infant out of every 10,000. Rotarix/RotaTeq: 2006, large pre-approval studies evaluated risk of intussusception. FDA review found both to be safe and effective with no increased risk of intussusception. Rotarix: 2010, post-marketing data in Mexico showed slight elevation in intussusception rate, but benefits of vaccination outweigh risk. FDA and CDC continue to recommend Rotarix and RotaTeq. 9

10. Current vaccine prices GSK and Merck vaccines in industrialized countries US$120-$200 per course South Africa public sector (birth cohort = 1 million) GSK: >$20 per 2-dose course PAHO Revolving Fund 2009 contracts (birth cohort = 8 million) GSK: $15.00 for 2-dose course Merck: $16.50 for 3-dose course GAVI Prices: Same price as PAHO 10

11. GAVI’s country commitment To satisfy country demand and introduce new vaccines to tackle rotavirus and pneumococcal disease, the GAVI Alliance needs to raise US$ 4.3 billion between now and 2015. 11

12. The need for new vaccines Two safe and effective commercial rotavirus vaccines exist, however Not yet widely available or affordable for low- income communities. Reduced efficacy in low-income settings. Slight elevation in intussusception risk. New rotavirus vaccines are needed to Create a sustainable market. Increase global supply. Reduce prices in order to ultimately satisfy global needs. 12

13. Advancing rotavirus vaccine development Goal: to accelerate the development and introduction of new safe, affordable, and effective rotavirus vaccines into the developing world through technical and financial support to emerging-country manufacturers. 13

14. Shared technology platform Several emerging-country manufacturers have licensed the bovine-human reassortant rotavirus vaccine (BRV) from the US National Institutes for Health. PATH created a “shared technology platform”—a toolbox of technologies, training, and common technical support to speed development and global access—for all companies actively developing the BRV. 14

15. Vaccine development partnerships 15

16. Pipeline RV vaccines - 2010 ResearchPhase 1 Phase 2 Phase 3Licensure3 Market B BI L (116116 E) LIBP BMC POLYVAC 16

17. Challenges in developing new rotavirus vaccines Need low cost vaccine Price highly dependent on volume for individual manufacturer Clinical development of new rotavirus vaccines Intussusception/post licensure surveillance Vaccine presentation and cold chain requirements/capacity 17

18. Can we achieve rotavirus vaccine immunization worldwide by 202X? Near term aspirations Optimize current vaccines for developing world Obtained lower prices Long term aspirations Develop new rotavirus vaccines Manufacture at high volume, low price, and optimal presentation 18

19. John Boslego, MD Director Vaccine Development Global Program jboslego@path.org 202-822-0033 www.path.org