GlaxoSmithKline Pandemic Influenza Portfolio

Transcription

1 GlaxoSmithKline Pandemic Influenza Portfolio Schladminger Gesundheitsgespräche 06. June 2009 Responding to the Pandemic Influenza Threat - WHO Recommended Strategic Actions Non-pharmacological measures Isolation and quarantine Border control Social distancing Hospital infection control Personal protection GSK s antiviral respirator mask Pharmacological measures Antivirals - Relenza Vaccines - Prepandrix & Pandemrix Surveillance Diagnostic tools Vaccines and antiviral drugs are the two most important medical interventions for reducing morbidity and mortality during a pandemic * Ref.: WHO. Communicable Disease Surveillance and Response Global Influenza Program. WHO/CDS/CSR/GIP/2005.8

2 Strategy to Build the Complete Portfolio Prepandrix and Pandemrix Only licensed pre-pandemic vaccine. Gives strong immunity against a broad range of H5N1 strains Antibiotic stockpiling Actiprotect Respirator The only respirator proven to prevent passage of live influenza virus through the mask Relenza The only influenza antiviral to which there is no known influenza A resistance Other essential medicine stockpiling GSK Diagnostic Potential for uniquely precise and rapid H5N1 diagnostic Pre-pandemic Vaccines and Antivirals Will Play Important Roles in Reducing the Impact in the First Months of a Pandemic Pre-pandemic vaccine (inducing cross-protection) World-Wide Pandemic Antiviral treatment and post-exposure prophylaxis Pandemic vaccine Antiviral treatment & exposure prophylaxis Time Pandemic vaccines will have value in protecting people from the second and third pandemic waves

3 Strategic Intent Complete Portfolio Prepandrix and Pandemrix Only licensed pre-pandemic vaccine. Gives strong immunity against a broad range of H5N1 strains Antibiotic stockpiling Actiprotect Respirator The only respirator proven to prevent passage of live influenza virus through the mask Relenza The only influenza antiviral to which there is no known influenza A resistance Other essential medicine stockpiling GSK Diagnostic Potential for uniquely precise and rapid H5N1 diagnostic Mechanism of Resistance to Oseltamivir Reproduced from Moscona A. N Engl J Med 2005;353: , with permission

4 Scientists Publishing in Nature Call for the Diversification of Antiviral Stockpiles Structural and enzymatic studies of oseltamivir-resistant H5N1 human isolates demonstrated retained susceptibility to Relenza The mechanisms of oseltamivir resistance are the same as those in H1N1 resistant isolates ' Our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir. It has been proposed that the closer neuraminidase inhibitors such as oseltamivir and zanamivir resemble the natural substrate the less likely they are to select-drug resistant mutant viruses that retain activity Collins PJ et al. Nature 2008; doi: /nature06956; Received 14 February 2008; Accepted 1 April 2008; Published online 14 May 2008 Simulation results: Antivirals Cases per 1000 R 0 =1.4 R 0 =1.7 Base (no intervention) 80% Targeted antiviral prophylaxis (TAP) 80% TAP + 50% prepandemic vaccination Ref.: Longini et al. Science 2005; 309:

5 Strategic Intent Complete Portfolio Prepandrix and Pandemrix Only licensed pre-pandemic vaccine. Gives strong immunity against a broad range of H5N1 strains Antibiotic stockpiling Actiprotect Respirator The only respirator proven to prevent passage of live influenza virus through the mask Relenza The only influenza antiviral to which there is no known influenza A resistance Other essential medicine stockpiling GSK Diagnostic Potential for uniquely precise and rapid H5N1 diagnostic GSK pre-pandemic vaccine - a two vial approach Antigen Adjuvant

6 Time Pandemic Preparedness Options World-wide H5N1 Pandemic Phase 3 Phase 4 Phase 5 Phase 6 : PANDEMIC Only reactive acquisition and use Might be too late 1 st 2 nd Protection * 3-4 weeks Stockpile, pandemic use (prime-boost) 1 st 2 nd Protection 4 6 months Stockpile, prepandemic and pandemic use (prime-boost) Stockpile, pre-pandemic use (prime-boost) 1 st 1 st 2 nd weeks to months 2 nd weeks to months Crossprotection Crossprotection 3 rd 3 rd Protection Protection * Ferguson et al.: Nature 2006; 442: Pre-pandemic vaccine Pandemic vaccine «But that starting vaccination as early as day 30 could bring the cumulative attack rate down to just 1%.» US Model No Vaccination 34% Vaccination from day 30 1% Vaccination from day 60 13% Vaccination from day 90 31% 0% 10% 20% 30% 40% Cumulative attack rate Policy of mass vaccination assuming 1% of the population can be vaccinated per day Most people are likely to be exposed to pandemic flu before they can be vaccinated Ref.: Ferguson et al. Nature 2006; 442(7101):448-52

7 Stockpiling a pre-pandemic vaccine is one of the key medical preparedness measures 3 key characteristics necessary A pre-pandemic vaccine offers potential for earlier protection, provided that 1. It has an acceptable safety profile and is well tolerated 2. It can be produced in sufficient quantities to immunise a critical mass of the population 3. It offers protection against a broad range of mutated variants of the threat virus GSK s candidate pre-pandemic H5N1 vaccine is an adjuvanted inactivated split vaccine Vaccine strain provided by NIBSC or other WHO reference laboratory. Strain used in vaccine: A/ Vietnam/1194/2004 A/Indonesia/5/ µg HA per AS adjuvant (oil-in-water emulsion, squalene, tween-80, and α- tocopherol) 2 vial system, multi presentation (10 s + preservative Thiomersal 5µg/) Egg-based manufacturing Manufactured in Germany, Canada,

8 The antigen and adjuvant components (enough for 10 s) must be mixed immediately prior to administration Adjuvant Antigen Withdraw 1 (0.5 ml) to administer (I.M.) Possibility to use Adjuvant System by local manufacturers Possibility to switch the Ag if there is an important change to the virus Cross-Immunogenicity after pre-pandemic vaccination post 2 (day 42) 3.75µg HA H5N1 A/Vietnam/1193/2004 AS-adjuvanted GMT. Heterologous strain A/Indonesia/5/2005 (Clade 2.1) n = 50 [95% CI] 80.3 [ ] Heterologous strain A/Turkey/1/2005 (Clade 2.2) n = 20 [95% CI] ] Heterologous strain A/Anhui/1/2005 (Clade 2.3) n = 20 [95% CI] 97.3 [ ] Seropositivity (%) 1: [ ] 100 [ ] 100 [ ] Seroconversion, 4fold increase (%) 77.1 [ ] 85.0 [ ] 75.0 [ ] 1. Leroux-Roels I. et al.: IX International Symposium on Respiratory Viral Infections. Hong Kong, March 3 6, unpublished data

9 Simulation results: Antivirals plus pre-pandemic vaccination give an optimal result Cases per 1000 R 0 =1.4 R 0 =1.7 Base (no intervention) 80% Targeted antiviral prophylaxis (TAP) 80% TAP + 50% prepandemic vaccination Ref.: Longini et al. Science 2005; 309: Strategic Intent Complete Portfolio Prepandrix and Pandemrix Only licensed pre-pandemic vaccine. Gives strong immunity against a broad range of H5N1 strains Antibiotic stockpiling Actiprotect Respirator The only respirator proven to prevent passage of live influenza virus through the mask Relenza The only influenza antiviral to which there is no known influenza A resistance Other essential medicine stockpiling GSK Diagnostic Potential for uniquely precise and rapid H5N1 diagnostic

10 ActiProtect & Virucoat are registered trademarks of the GSK Group of companies in the US & EU How Actiprotect works Electrostatic non-woven layer filters fine particles and aerosols (N95/FFP2 certification) Face side Polypropylene layer absorbs moisture Air Contaminant Patent pending Virucoat inactivates influenza virus Inner and outer fabric layers provide structure, durability, and comfort against skin PPE/COE/1208/0010/01 - January 2009

11 Mechanism of Action Surfactant aids wetting / emulsification, allows rapid access to acid Acid environment mimics uncoating process inside cell Low ph Conformational change of HA Proton influx Low ph-induced structural changes of the capsid Denaturation like Capsid Uncoating Inactivation Antiviral Efficacy Against Other Influenza Subtypes Influenza subtypes tested to date Subtype H5N1 H2N2 H3N2 H5N9 N/A B Strain NIBRG-14 VNH5N1-PR8/CDC-RG J 305 Hong Kong 8/68 Turkey A/Wisc/68 Myna A/Mass/71 Allen > 3 log Antiviral Efficacy

12 Strategy to Build the Complete Portfolio Prepandrix and Pandemrix Only licensed pre-pandemic vaccine. Gives strong immunity against a broad range of H5N1 strains Antibiotic stockpiling Actiprotect Respirator The only respirator proven to prevent passage of live influenza virus through the mask Relenza The only influenza antiviral to which there is no known influenza A resistance Other essential medicine stockpiling GSK Diagnostic Potential for uniquely precise and rapid H5N1 diagnostic Danke für Ihre Zeit & Aufmerksamkeit Proprietary and Confidential. Not for Distribution without GSK s Permission

13 Back-up Immuno against homologous strain Adults 4 vaccines fullfill all the three CHMP criteria for adults GSK, Sanofi adjuvanted, Novartis adjuvanted and Sinovac adjuvanted GSK vaccine lowest of antigen (3.75 mcg) highest SPR (94.3%), SCR (93.7%) and SCF (39.8) compared to the Novartis MF59 SCF 39.8 vs 7.85 Parameter used as legitimate comparator of immunogenicity across trials (i.e. no head to head)

14 SPC Prepandrix TM SPC Focetria TM