Sanofi Pasteur, the vaccines division of the sanofi-aventis Group (EURONEXT: SAN and NYSE: SNY), announced today the results of a clinical trial of its investigational Fluzone® Quadrivalent (Influenza Virus Vaccine) compared to the currently licensed Fluzone (Influenza Virus Vaccine). Data from the Phase II trial assessing the immunogenicity and safety of the investigational quadrivalent vaccine were presented at the 48th Annual Meeting of the Infectious Diseases Society of America in Vancouver, British Columbia.
In this study, sponsored by Sanofi Pasteur, quadrivalent inactivated influenza vaccine (QIV) containing two strains of type A (H1N1 and H3N2) and two strains of type B (one each from the Yamagata and Victoria lineages) was evaluated in comparison to two trivalent seasonal influenza vaccines (TIV) each containing the two strains of type A plus one of the two type B strains. The data indicated that the QIV vaccine was immunologically non-inferior to TIV for all strains and the safety profiles of QIV and TIV did not materially differ. Moreover, QIV induced responses to both B lineage strains simultaneously.
"Based on the data from this trial, Sanofi Pasteur plans to proceed with Phase III clinical trials of Fluzone Quadrivalent vaccine this fall," said Wayne Pisano, President and Chief Executive Officer, Sanofi Pasteur. "We believe that Fluzone Quadrivalent vaccine could be an important vaccine for public health that may help reduce overall morbidity and mortality caused by influenza."
Since influenza B Victoria lineage re-emerged worldwide in 2001-2002, both Victoria and Yamagata lineages have circulated with varying prevalence, making it difficult to predict the next season's dominant lineage. Even in years where there was a good match, some influenza disease was caused by the B lineage omitted from the vaccine. This raised the hypothesis that the addition of a second B lineage strain to expand the licensed trivalent influenza vaccine to a quadrivalent vaccine could reduce influenza morbidity and mortality.
Study Design and Results
The immunogenicity and safety of the quadrivalent influenza vaccine was assessed in adults 18 years of age and older in comparison to the Fluzone vaccines licensed for use during the 2008-2009 and the 2009-2010 seasons. This study design took advantage of the fact that the 2008-2009 and 2009-2010 TIVs contained identical A strains, but B strains of opposite lineages. Adult study participants (n = 570) were randomized to receive one of three study vaccines: 2008-2009 TIV (n = 190), 2009-2010 TIV (n = 190) or QIV (n = 190); and were stratified into two age groups: 18 to 61 years of age, and 61 years of age and older. Blood specimens were collected pre-vaccination and 21 to 28 days post-vaccination and standardized hemagglutination inhibition (HAI) antibody assays were performed by persons blinded to vaccine assignment to determine immunogenicity.
The immunogenicity endpoints of the study were: geometric mean HAI antibody titers (GMTs), the percent of study participants with a 4-fold rise of HAI titers pre- to post-vaccination and the percent of participants with post-vaccination HAI titers greater than or equal to 1:40. Safety was an observational objective with immediate reactions monitored in the clinic for 20 minutes post vaccination, solicited systemic and injection-site reactions recorded by participants on diary cards for three days post-vaccination and unsolicited adverse events (AEs) and serious adverse events (SAEs) reported by participants from vaccination to second visit (21 to 28 days post-vaccination).
The safety profiles of QIV and TIV did not materially differ as assessed by rates of solicited injection-site and systemic reactions, unsolicited AEs and SAEs. For all groups, the most frequently reported solicited injection-site reaction was pain and the most frequently reported solicited systemic reactions were myalgia, headache and malaise. In the evaluation of immunogenicity, HAI antibody responses to QIV were comparable to both licensed TIVs as assessed by GMTs, 4-fold rise rates and the percent of participants with titers greater than or equal to 1:40. QIV induced statistically non-inferior GMT responses to each A strain (H1N1 and H3N2) and each B lineage strain (Victoria and Yamagata) compared with the control TIVs containing the respective strains.
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