Jesse L. Goodman, M.D., M.P.H. Chief Scientist Food and Drug Administration November 14, 2012

1. VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEEThe Public Health Need for Pandemic Influenza Vaccines Jesse L. Goodman, M.D., M.P.H. Chief Scientist Food and Drug Administration November 14, 2012

2. Public Health Impacts of 2009 Pandemic Influenza A (H1N1) and of immunization • Global estimates of ~ 300,000 deaths from even this “mild” pandemic • Estimated 61 million cases, 275,000 hospitalizations and 12,500 deaths in U.S. • U.S. estimated benefits from immunization, even though vaccine available late to impact first wave: • reduction of 713,000 to 1.5 million in cases • 3900-10,400 hospitalizations, and • 200-520 deaths • Dawood et al, Lancet Infectious Diseases 2012; 12; 687-95 • http://www.cdc.gov/h1n1flu/pdf/Exact%20Numbers_AprilN.pdf • Morbidity and Mortality Weekly Report. Notice to readers: Revised estimates of the public health impact of the 2009 pandemic influenza A (H1N1) vaccination. September 30, 2011/60(38); 1321

3. Factors Contributing to Successful Pandemic Influenza Vaccine Preparedness and Response • Extensive coordination between federal partners, international stakeholders, academia and industry to identify and distribute virus strains, manufacture candidate vaccines, and conduct needed studies • FDA approval of monovalent pandemic vaccine as a “strain change” using licensed manufacturing processes under established regulatory frameworks • HHS investments in pre-pa Extensive coordination between federal partners, international stakeholders, academia and industry to identify and distribute virus strains, manufacture candidate vaccines, and conduct needed studies

4. The Risk of Pandemic Influenza The risk of pandemic influenza remains serious • The timing and severity of future influenza pandemic cannot be predicted • H5N1 persists – other serotypes remain a potential threat (witness recent H3N2 swine related outbreaks) and new virus types may well arise unpredicted • For vaccines primarily circulating in other species, such as avian and swine origin viruses, human cases provide opportunities for mutation and reassortment which may enhance transmissibility among humans and increase risks of a pandemic. • Vaccines can protect both immunized individuals and reduce transmission to others and as such present an important intervention against pandemic influenza, particularly when available early in a pandemic, and given limitations of and potential resistance to antivirals. 1918 1956 1968 2009 ? Spanish Asian Hong Kong Swine Flu H5N1 Flu Flu Flu (H1N1) 25,000,000 70,000 34,000 +450 +359 deaths deaths deaths deaths deaths Since 2003

5. Confirmed Human Cases of Avian Influenza A (H5N1) Reported to WHO, 2003-2012 Unlike 2009 H1N1, H5N1 currently has a low human-to-human transmission rate but a very high mortality rate; more than half of recent human cases of documented infection H5N1 avian influenza were fatal (WHO, 2006). Also unlike H1N1, H5N1 is poorly immunogenic and the population does not have background immunity Source: WHO/GIP, data in HQ as of 10 August 2012

6. Pandemic Influenza Preparedness • FDA continues to work with its government partners, e.g., the National Institutes of Health (NIH), the Centers for Disease Control (CDC) and the Department of Health and Human Services (DHHS), and with the vaccine industry to facilitate the licensure and availability of safe and effective vaccines against potential pandemic influenza strains. • There is currently one US-licensed pandemic H5N1 influenza virus vaccine manufactured by sanofi pasteur • Unadjuvanted, immunization which requires two 1 ml IM injections of 90 ug • Included in the US Strategic National Stockpile • The high dose of H5 antigen required for non-adjuvanted H5N1 vaccines presents a significant impediment both to vaccine stockpiling and to rapidly producing sufficient vaccine for an effective response to a pandemic

7. Pandemic Influenza Preparedness • Thus, there is a need for adjuvanted influenza vaccines with enhanced immunogenicity to expand US pandemic vaccine stockpiling and surge capacity (e.g., allow reduced antigen use/dose) and speed the production and availability of sufficient doses in a pandemic • While nonadjuvanted vaccines are safe and effective, their efficacy is not optimal. • Novel adjuvants may enhance both the immune response to a given strain as well as the breadth of immunity, producing additional benefits, for example increasing protection against “drifted” strains

8. Q-Pan H5N1 pandemic influenza vaccine, adjuvanted • US government, through ASPR/BARDA, has supported vaccine manufacturers to develop candidate H5N1 influenza virus vaccines with antigen sparing potential • Today we will be considering data to support the safety and immunogenicity of an adjuvanted pandemic influenza vaccine against H5N1 influenza virus, Q-Pan • Split virion (A/Indonesia/5/2005) inactivated hemagglutinin antigen • AS03 adjuvant system • manufactured by Glaxo Smith Kline • same manufacturing platform as used for licensed seasonal inactivated influenza vaccine, FluLaval.

9. Q-Pan H5N1 pandemic influenza vaccine, adjuvanted • This vaccine is intended to support pandemic preparedness and response, and has the potential to facilitate the more rapid availability of a larger number of vaccine doses, as well as the more rapid onset of an immune response of enhanced breadth • If licensed, this vaccine will become the first FDA approved adjuvanted influenza vaccine available in the U.S.