Vaccine Preventable Diseases: Pneumococcal Vaccine An Opening Wedge for New Vaccine Introduction and Development Presented by: Christopher W. Woods Slides Prepared by Orin Levine Executive Director, International Vaccine Access Center Professor, International Health Johns Hopkins Bloomberg School of Public Health

Other Remedies of the Time

Vaccine History 1794-Dr. Edward Jenner 1952-Polio vaccine 1963-Measles vaccine 1974-Expanded Program on Immunization Measles, Polio, DPT 1980-Smallpox Eradication 20??-Polio Eradication

Expanded Program on Immunization

Why is new vaccine introduction important? Child mortality rates remain unacceptably high in many countries Injustice Expensive Destabilizing

Why is new vaccine introduction important? A Global Forecasting Model of Political Instability by Goldstone et al. “lower-income countries showed a higher risk of instability. This is one of the best-established results in the conflict literature, of course, so we sought to improve on it. … Yet no model, no matter how complex, performed significantly better than models that simply used infant mortality (logged and normalized) as a single indicator of standard of living.”

Why is new vaccine introduction important? Causes of 8.8M child deaths, 2008 (Black et al. Lancet 2010) Pneumonia Pertussis Measles Meningitis Malaria Diarrhea 1.58M pneumonia deaths among children < 5 years AIDS

Annual deaths & deaths averted by vaccines 2.5mil deaths averted 2.5mil deaths Source: W. Orenstein, Gates Foundation; WHO, Burden of Disease 2004, released 2008

Why is new vaccine introduction important? Vaccines can contribute to improving child survival, economic development, & national security Vaccines available vs leading killers of children New vaccines available shortly Substantial existing delivery program

Consider Hib conjugate vaccine Hib – a leading cause of childhood meningitis and pneumonia worldwide Safe, effective vaccine used since 1990 in USA and other rich countries

If you build it, they will come… It worked in the movie but does it work for new vaccine introduction?

Global Hib Vaccine Uptake High and Low Income Countries

Vicious Cycle That Delayed Hib Vaccines 1) Uncertainty about demand in developing countries leads industry to limit investments in capacity Uncertain demand Limited supply Higher price 3) Higher prices keep developing countries uncertain about demand and donors uncertain about financing needs 2) Limited vaccine supply keeps prices relatively high This is the reason for the delay – uncertain demand leads to limited supply which in turn keeps prices too high for developing countries to afford and demand, and donors uncertain about financing needs

Saving lives requires finding “solution space” Industry willing to supply Solution space where lives are saved Donors & countries willing to pay Countries willing & able to introduce

Pneumococcal conjugate vaccine Licensed in 2000 Leading cause of childhood pneumonia & meningitis deaths Proven safe, effective 7 deaths prevented per 1000 vaccinated in African trial of 9v vaccine Cutts F et al Lancet 2005

Global Alliance for Vaccines and Immunisation (GAVI): PneumoADIP Mission: To improve child health and reduce mortality by accelerating the evaluation of and access to new, life-saving pneumococcal vaccines for the world’s children. Research & Surveillance Communications Vaccine Access & Implementation Project Administration Improving child health by accelerating access to vaccines To avoid history repeating it self, in 2003, GAVI created the PneumoADIP, a 5-year, $30M grant ( read ) The PnemoADIP is a small, dedicated team located at JHU that works in partnership with WHO

PneumoADIP strategic goals Strategic Goal 1: Provide information that enables national decision-makers, the GAVI board and its partners to make an evidence-based decision regarding the use of vaccine. Strategic Goal 2: Accelerate the availability of affordable, new vaccines appropriate for use in developing countries.

“Solution space” status: 2003 Donors/ Countries Willing to Finance No financing for vaccine purchase “Too expensive to manufacture/Never affordable” Industry Willing to Supply Supply limited; just enough for rich countries Vaccines $60/dose; doesn’t include vial sizes countries want Lets start with the money – GAVI has committed 100 million to an investment in Pneumococcal vaccine, this includes vaccine purchase Heavy weight donors in the G7 and Gates Foundation have pledged 1.5 billion in an advance market commitment to subsidize the purchase of Pneumococcal vaccines for GAVI countries The supply outlook looks good Routine use of pneumococcal conjugate vaccine, including the available 7-valent vaccine, should begin as soon as possible Countries where 7-valent vaccine is expected to have substantial health impact include those with a high burden of pneumonia and evidence that the serotypes included in the vaccine are responsible for a large proportion of IPD. Countries Willing to Introduce No WHO recommendation No WHO disease burden estimates by country

Surveillance documents disease patterns

Epidemiology, effectiveness, & economics ?How much pneumococcal disease do we have in children? WHO Disease Burden Estimates by Country ?How well with the vaccine match our serotypes? Serotype Distribution by Region

Epidemiology, effectiveness, & economics ?How cost-effective will the vaccine be in our country? Cost-Effectiveness & Health Impact Estimates by Country On-line web tool for national estimates using local data

Global Vaccine Policy at WHO Strategic Advisory Group of Experts

Pneumonia attention does not equate with disease burden Volume of hits compared to number of child deaths per disease | Source: Projections based on Google Search, July 2006 and The World Health Report 2005 – Make Every Mother and Child Count Pneumococcal disease coverage remained behind HIV/AIDS, TB, malaria and measles, despite the burden of pneumococcal disease being greater. HIV/AIDS consistently dominated the media agenda, attracting almost twice as much coverage as all other diseases combined.

World Pneumonia Day Coalition http://worldpneumoniaday.org/

Illustrative

Illustrative

Investment case Approved! By GAVI Board Nov 2006

Major PneumoADIP accomplishments “GAVI’s efforts have truly accelerated the demand for pneumococcal vaccines.” GAVI Phase 2 Independent Evaluation Research & Surveillance >50 countries with quality surveillance Disease burden, serotype, and cost-effectiveness estimates for every country Successes in collaboration with WHO Communications Increased donor awareness Increased country level recognition of vaccine value Established new practices and standards Access & Implementation Strategic demand forecast Affordable, sustainable vaccine supply Better vaccines Investment cases for >$1.6 billion

“Solution space” status: 2008 Donors/ Countries Willing to Finance GAVI Board endorsed Investment Case for Pneumococcal Vaccines $1.5 billion for an Advance Market Commitment for pneumococcal vaccines Multinational & emerging manufacturers now committed to supply GAVI countries Vaccines will have high serotype coverage, affordable price, and good vial size Industry Willing to Supply Lets start with the money – GAVI has committed 100 million to an investment in Pneumococcal vaccine, this includes vaccine purchase Heavy weight donors in the G7 and Gates Foundation have pledged 1.5 billion in an advance market commitment to subsidize the purchase of Pneumococcal vaccines for GAVI countries The supply outlook looks good Routine use of pneumococcal conjugate vaccine, including the available 7-valent vaccine, should begin as soon as possible Countries where 7-valent vaccine is expected to have substantial health impact include those with a high burden of pneumonia and evidence that the serotypes included in the vaccine are responsible for a large proportion of IPD. Countries Willing to Introduce WHO recommends pneumococcal vaccine in routine immunization programs 8 approvals, 3 conditional approvals & 34 expressions of interest

Number of Countries per year GAVI Pneumo: actual, recommended and forecasted introductions (Sept. 2010) Burundi Benin CAR Cameroon DR Congo Ethiopia Gambia Guyana Honduras Kenya Madagascar Mali Malawi Nicaragua Pakistan Rwanda Sierra Leone Yemen Without financial constraints Number of Countries per year Actual Recommended Forecast Slide courtesy Lauren Franzel, PATH

Pneumococcal Vaccine Access Accelerated, Compared to Hib

The value of accelerated vaccine introduction Source: GAVI website

COI Results - Health Impact of Vaccine Scale-up 6.4 million Deaths Averted 426 million Cases Averted To determine the economic benefit of introducing and scaling up coverage of the six vaccines, we first had to project the health impact: 6.4 million child deaths would be averted in the 72 GAVI eligible countries over 10 years A majority of the averted deaths are due to pneumonia and diarrhea prevention primarily from the introduction and scale-up of PCV and rotavirus vaccines Important to note that vaccines against pertussis, measles and certain causes of meningitis (hib) are already introduced in most countries, so the health impact of scaling their coverage up to 90% will be lower than vaccines that have yet to be introduced. 426 million cases averted The share of cases prevented due to rotavirus vaccine is substantially larger than the share of deaths prevented due to the higher incidence and lower severity of diarrhea compared to other syndromes such as meningitis and pneumonia 63,000 severe disabilities due to meningitis sequelae would be prevented from hib and pcv introduction and scale-up 63,000 Disabilities Averted Due to meningitis prevention 72 GAVI Countries; 2011-2020 (inclusive) Source: Stack ML, et al. Health Aff (Millwood). 2011;30(6):1021-1028.

Immediate Economic Benefits Preventing illness could save $6.2 billion ($4.8-9.1 b) in treatment costs and $1.2 billion ($0.7-1.4 b) in lost output of caretakers The health impact of vaccines directly results in both immediate and long-term economic benefits The immediate savings that local governments and households would realize from vaccines could total $7.4 billion ($6.2 from averted treatment costs and $1.2 from lost wages of caretakers). – could total over $800 million annually when coverage of all vaccines reach 90% A majority of these benefits are again from diarrhea and pneumonia prevention. The substantial economic savings from a vaccine against malaria becomes apparent after it is introduced in 2015 and scaled up to 90% by 2020. Source: Stack ML, et al. Health Aff (Millwood). 2011;30(6):1021-1028.

Long-term Economic Benefits Future economic output increased by $144 billion ($120-168B) - Totaling $151 billion ($131-176B) in immediate & long-term benefits However, the vast majority (95%) of the economic benefit of vaccines is realized over the long-term. While $7.4 billion in immediate savings could be realized over the next ten years, reduced mortality and morbidity due to vaccine scale-up could result in $144 billion in increased income over the lifetime of those immunized between 2011-2020. The majority of these economic benefits are realized in three countries (India, Nigeria, Angola). This is not only due to the large populations of India and Nigeria, but also to the fact that both countries have yet to introduce Hib vaccine and that Angola has a relatively high average income. Immediate Benefits = Treatment costs + Caretaker Productivity Long-term Benefits = Morbidity Productivity + Mortality Productivity Source: Stack ML, et al. Health Aff (Millwood). 2011;30(6):1021-1028.

Main takeaways Dedicated team Use evidence to set consensus & policies Team that “sweats the details” every day Use evidence to set consensus & policies Need “push” to move into implementation Strategic demand forecast Lays out “what will it take” for each stakeholder

Evidence to policy to implementation Disease burden Efficacy Cost-effectiveness Serotypes Safety Establish & organize evidence Recommendations Financing Establish supportive global policies Evidence-driven advocacy Vaccine impact Systems (including surveillance) Translate policies into local action Levine OS et al. Curr Op Infect Dis 2010

Moving from policy to implementation Can feel like it’s a lot to handle http://www.youtube.com/watch?v=8NPzLBSBzPI

Opportunities & Challenges Impact on child health & economies Success breeds success Improved equity Biggest ever coordination needed Maintaining focus in face of competing priorities Economic setbacks

For more information, please visit Thank you! For more information, please visit www.jhsph.edu/ivac www.preventpneumo.org www.sabin.org/PACE Thank you for your interest in helping us find Pneumo.

Global Pneumococcal Vaccine Uptake High & Low Income Countries

Historical Hib Introduction by Income Group Source: Johns Hopkins University IVAC. VIMS Report: Global Vaccine Introduction (August, 2011).

Global PCV Introduction Status Source: Johns Hopkins University IVAC. VIMS Report: Global Vaccine Introduction (August, 2011).

GAVI Countries PCV Introduction Status Source: Johns Hopkins University IVAC. VIMS Report: Global Vaccine Introduction (August, 2011).

Pneumococcal is learning from Hib yrs since licensure Pneumo Years accelerated Licensure 1990 2000 Africa trial 1993 3 1998 -2 5 Asia trial 8 2002 2 6 Financing 10 2006 4 ADIP created 2005 15 2003 12 1st WHO rec 2nd WHO rec 16 2007 7 9 Procurement 2008 Significant acceleration of “evidence”, recommendations, advocacy and financing but little improvement in access to supply and Unicef procurement

More than 40 countries by 2015 Following the May 2011 round, almost 70% of GAVI countries have sought support for PCV introduction. A total of 37 GAVI-eligible countries have been approved for GAVI support to introduce pneumococcal conjugate vaccine into their national immunisation programmes. With an additional 18 countries approved as of September 2011, pneumococcal vaccines will soon be administered in more than half of GAVI eligible countries. This is an unprecedented rapid ramp up. To date, 14 countries in the developing world have begun the introduction of pneumococcal vaccines. By rapidly scaling up the number of countries and the number of children receiving the vaccines, GAVI and its partners can avert over 650,000 deaths by 2015 and up to seven million deaths by 2030.

Supplier perspective: Volumes / yr

Country/donor perspective: $ / year Illustrative