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

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 I ADDED SOME ADDITIONAL STATISTICS, REFERENCES AND TOOK OUT ANTIVIRAL INFO AS CONFUSING Important to note that these impacts would be much greater with earlier vaccine availability, – relevant to adjuvanted vaccine where more doses may be available earlier, and impacts may also be greater with a pandemic of greater severity, and if adjuvanted vaccine more effective

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 IS IT OK TO SAY THAT WE WOULD ANTICIPATE SIMILAR STRAIN CHANGE APPROACH FOR SUBSEQUENT ADJUVANTED PANDEMIC STRAINS?

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

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 Year Cases Deaths 2003 4 2004 46 32 2005 98 43 2006 115 79 2007 88 59 2008 44 33 2009 73 2010 48 24 2011 62 34 2012 30 19 Total 608 359

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 I added something re existing vaccines not optimal and potential benefits of adjuvants

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

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. Changed presenting to considering

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. I ADDED AGAIN RE NATURE OF IMMUNE RESPONSE WON’t IT BE THE FIRST LICENSED ADJUVANTED FLU VACCINE PERIOD? AND THE FIRST LICENSED VACCINE USING AN OIL AND WATER ADJUVANT? WILL IT BE COMMERCIALLY AVAILABLE?