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Novartis Vaccines - Influenza A H1N1v vaccine development

Novartis Vaccines - Influenza A H1N1v vaccine development. DHHS supported influenza cell culture vaccine production facility, Holly Springs, N Carolina. Theodore F Tsai MD MPH July 23, 2009. Agenda. Novartis portfolio of influenza vaccines MF59 ™ oil-in-water emulsion adjuvant

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Novartis Vaccines - Influenza A H1N1v vaccine development

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  1. Novartis Vaccines - Influenza A H1N1v vaccine development DHHS supported influenza cell culture vaccine production facility, Holly Springs, N Carolina Theodore F Tsai MD MPH July 23, 2009

  2. Agenda • Novartis portfolio of influenza vaccines • MF59™ oil-in-water emulsion adjuvant • H5N1, MF59-adjuvanted vaccine, egg-derived (AFLUNOV®/FOCETRIA®) • H5N1, MF59-adjuvanted vaccine, cell culture-derived (OPTAFLU® platform) • H1N1v vaccine clinical studies • U.S.-licensed Fluvirin® egg-based platform • Europe-licensed/investigational platforms • FOCETRIA, egg-derived • Cell culture-derived • H1N1v product supply

  3. Novartis seasonal and pandemic influenza vaccines

  4. 97 97 97 97 129 140 100 100 89 89 117 120 80 80 100 60 60 80 67 Seroprotection (%) Seroconversion (%) 60 Geometric mean ratio (D43/D1) 40 40 40 20 20 20 0 0 0 Children 3-<9 y (n=91) Adolescents 9-17 y (n=89) Toddlers 6-<36 mo (n-131) Children 3-<9 y (n=91) Adolescents 9-17 y (n=89) Toddlers 6-35 mo (n=134) Children 3-8 y (n=91) Adolescents 9-17 y (n=89) Toddlers 6-<36 mo (n=134) CHMP benchmarks are for adults Multiple potential advantages of MF59 adjuvant in pandemic and seasonal influenza vaccines GMTs 688 585344 MF-59 oil in water emulsion adjuvant • A component of seasonal influenza vaccine FLUAD* for adults >65 years old, licensed since 1997 • More than 45 million doses distributed • Controlled clinical trial data on >33,000 subjects • Ongoing FLUAD - active/placebo controlled efficacy trial in 3,000 6-36 month old subjects • No safety signals in either the clinical trial database or in pharmacovigilance. • Adjuvanted vaccine provides higher and broader antibody responses • Cross-reactive antibody responses against antigenically drifted seasonal strains • Broadly cross-reactive responses against the majority of H5N1 subclades • Allows for antigen sparing Seroprotection rate Seroconversion rate HI antibody fold-rise • HI antibody response against an homologous H5N1 Vietnam strain at day 43 • Vaccine contained 7.5 µg HA and full MF59 dose AFLUNOV is not a licensed vaccine :NCT00537524 Vesikari T (submitted)

  5. Antigen- and MF59 dose-sparing of MDCK cell culture-derived-Indo/5/2005(H5N1) subunit vaccine Day 43 HI responses, 21 days after second dose, in healthy young adults MF59* *Compared to MF59 content in EMEA- licensed MF59-adjuvanted seasonal influenza vaccine HA antigen (µg dose) N 55 55 53 52 51 51 53 52 58 50 59 47 NCT00812019 Keitel W et al (submitted)

  6. MF59 Clinical DatabaseTotal number of subjects in controlled clinical studies (as of June 2009) • No increase in risk of SAEs, new onset of chronic disease, autoimmune disorders in pooled analysis of 94 trials with 6 month follow-up - safety analysis submitted to CBER • Pediatric and H5N1 trials under oversight of Independent Data Monitoring Committees • Large scale observational study of 75,000 senior adults, Italy Novartis Data on File

  7. Agenda • Novartis portfolio of influenza vaccines • MF59 oil-in-water emulsion adjuvant • H5N1 vaccine, MF59 adjuvanted, egg-derived (AFLUNOV/FOCETRIA) • H5N1 vaccine, MF59 adjuvanted, cell culture-derived (OPTAFLU platform) • H1N1v vaccine clinical studies • U.S.-licensed Fluvirinegg-based platform • Europe-licensed/investigational platforms • FOCETRIA, egg-derived • Cell culture-derived • H1N1v product supply

  8. Fluvirin H1N1v Vaccine Overview of clinical trials under US IND • Safety monitoring for one year • Blood samples for clinical laboratory safety measurements during treatment period • Immunogenicity – HI responses • Various intervals between Dose 1 and Dose 2 • Weekly samples to detect early responses • Additional trials and observational studies under discussion • Pilot and pivotal studies

  9. Fluvirin H1N1v - Pilot clinical trialTrial design • First subject, first visit ~Aug 17 • First interpretable serological result, dose 1 – mid-Sep • First interpretable serological result, dose 2 – late-Sep • Completed Clinical Study Report – mid-Nov

  10. Adult & elderly pivotal trial: N = 2,380 Pediatric trial, 3y – 9 years: N = 1,190 Fluvirin H1N1v – Vaccine registration studiesTrial design • First subject, first visit ~ Aug 27 • First interpretable serological result, dose 1 – late-Oct/early Nov • First interpretable serological result, dose 2 – early Nov/mid Nov • Completed Clinical Study Report – mid-Dec/late-Dec 1. Antigen doses are nominal 2. 3/4 dose refers to MF59 dose including 7.31 mg squalene and full dose refers to MF59 dose including 9.75 mg squalene. “Full dose” refers to the dose contained in the licensed seasonal trivalent influenza vaccine, Fluad® 3. 75% dose refers to MF59 dose including 7.31 mg squalene and 100% dose refers to MF59 dose including 9.75 mg squalene; quantities relate to the content of MF59 in the licensed seasonal influenza vaccine, Fluad®

  11. H1N1v vaccines in EuropeFocetria and Cell derived-vaccines -Trial Overview

  12. Agenda • Novartis portfolio of influenza vaccines • MF59 oil-in-water emulsion adjuvant • H5N1 vaccine, MF59 adjuvnated, egg-derived (AFLUNOV/FOCETRIA) • H5N1 vaccine, MF59 adjuvanted, cell culture-derived (OPTAFLU platform) • H1N1v vaccine clinical studies • U.S.-licensed Fluvirin egg-based platform • Europe-licensed/investigational platforms • FOCETRIA, egg-derived • Cell culture-derived • H1N1v product supply

  13. H1N1v Vaccine Supply • Novartis has committed Liverpool site to produce US supply through end of year • Bulk production has commenced already • Goal is for 90M 15 µg bulk doses produced by Nov 30, based upon yields • Fill / finish production will proceed upon U.S. Government formulation decision • First doses available 4-6 weeks after fill / finish decision • Antigen production yields are below levels for seasonal strains • NVD continues to optimize process • Will also evaluate alternate strains / reassortants to improve yield

  14. Summary • Dose ranging clinical trials of H1N1v vaccines, with/without MF59 adjuvant, produced on • Egg-based Fluvirin platform – US • Egg-based Focetria platform - Europe • Cell-derived platform - Europe • Data from the Fluvirin-H1N1v pilot study provided on a rolling basis • Preliminary serological results of dose 1, 1 week response available mid-Sep • Data on all IND studies projected for mid-Nov – late-Dec • Data from first cell culture-derived vaccine pilot study projected mid-Sept

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