Clinical Trials

* On August 13, 2014, Sanofi Pasteur, the vaccines division of Sanofi, announced that The New England Journal of Medicine published positive results from a large-scale, multi-center efficacy trial, which found that Fluzone® High-Dose  was more efficacious in preventing influenza in adults 65 years of age and older compared to standard-dose Fluzone® vaccine. Fluzone® High-Dose vaccine was found to be 24.2 percent (95% CI, 9.7 to 36.5) more effective in preventing influenza relative to standard-dose Fluzone® vaccine for the primary endpoint, indicating that about one in four breakthrough cases of influenza could be prevented if Fluzone® High-Dose vaccine were used instead of the standard dose Fluzone vaccine in this population. Additionally, relative efficacy was 35.4 percent (95% CI, 12.5 to 52.5) in an analysis restricted to influenza cases caused by vaccine-similar strains.
Investigators compared the vaccine’s efficacy in a large-scale, randomized, double-blind, trial that spanned two influenza seasons. The trial enrolled nearly 32,000 participants; 14,500 and 17,489 adults 65 years of age and older during the 2011 2012 and 2012-2013 influenza seasons, respectively, from 126 research centers in the United States and Canada. The primary endpoint of the study was the occurrence of laboratory-confirmed influenza at least 14 days post-vaccination caused by any influenza viral type or subtype. Investigators determined that participants in the Fluzone High-Dose vaccine group were less likely to get the flu than those in the standard-dose Fluzone vaccine group. Specifically, 228 people in the Fluzone® High-Dose vaccine group (1.43 percent) and 301 people in the standard dose Fluzone® vaccine group (1.88 percent) had laboratory-confirmed influenza, demonstrating that Fluzone® High-Dose vaccine was 24.2 percent (95% CI, 9.7 to 36.5) more effective in preventing influenza than standard-dose Fluzone® vaccine. Additionally, researchers determined that most rates for pneumonia, cardio-respiratory conditions, hospitalizations, non-routine medical office visits and medication use were lower for the Fluzone High-Dose vaccine group compared to the standard dose Fluzone® vaccine group.
The full results from this trial formed the basis for a regulatory submission to the FDA late last year to seek a modification to the Prescribing Information for Fluzone® High-Dose vaccine reflecting the improved efficacy compared to standard dose Fluzone® vaccine in adults 65 years of age and older. Sanofi Pasteur anticipates a decision later this year. The study safety data were consistent with previous Fluzone® High-Dose vaccine studies. During the surveillance period (approximately six to eight months post-vaccination each season), 1,323 (8.27 percent) and 1,442 (9.02 percent) people who received Fluzone® High-Dose vaccine and standard-dose Fluzone vaccine, respectively, experienced at least one serious adverse event (SAE). Overall, the risk of experiencing at least one SAE was lower for the Fluzone® High-Dose vaccine group compared to the standard-dose Fluzone® vaccine group (relative risk 0.92, 95% CI 0.85-0.99), suggesting that Fluzone® High-Dose vaccine may protect against the occurrence of influenza-related serious events. Three SAEs in the Fluzone High-Dose vaccine group were deemed vaccine-related; none resulted in discontinuation from the study. Cardiac disorders and infections were the most frequent types of SAEs in both groups. There were a total of 83 deaths in the Fluzone® High-Dose vaccine group and 84 deaths in the standard-dose Fluzone vaccine group during the six-month surveillance period, none of which were considered by the investigators as related to vaccination.
Fluzone® High-Dose vaccine was licensed in the United States by the FDA in December 2009 based on the vaccine’s safety profile and superior immunogenicity compared to standard-dose Fluzone® vaccine. Fluzone® High-Dose vaccine contains 60 ?g of influenza hemagglutinin antigen per strain as compared to 15 mcg of hemagglutinin antigen per strain in standard-dose Fluzone® vaccine. Post-vaccination, Fluzone® High-Dose vaccine induces significantly higher antibody responses compared to standard-dose Fluzone® vaccine.

* On August 26, 2013, Sanofi Pasteur, the vaccines division of Sanofi, has announced topline results of a large-scale, multi-center efficacy trial in people 65 years of age and older showing a superior clinical benefit of Fluzone® High-Dose (Influenza Virus Vaccine) relative to the standard dose of Fluzone® vaccine in preventing influenza. This announcement reflects the positive findings related to the primary endpoint for the study population. Further data analyses of secondary endpoints are ongoing, including an evaluation of the relative efficacy based on the match of the vaccine strains to circulating influenza virus strains. Sanofi Pasteur anticipates submitting the full clinical study report to the FDA for review by early 2014 and will seek a modification to the label for Fluzone® High-Dose vaccine reflecting the superior efficacy data in adults 65 years of age and older.

In the study, Fluzone® High-Dose vaccine was 24.2 percent more effective in preventing influenza in adults 65 years of age and older than Fluzone vaccine. The results met the pre-specified primary objective of the study, demonstrating statistically superior efficacy for Fluzone® High-Dose vaccine. Additionally, the study results suggested consistent clinical benefit across the study years, influenza virus types, clinical illness definitions, and laboratory methods of influenza confirmation. This large, multi-year trial also reaffirmed the safety of Fluzone® High-Dose vaccine as demonstrated in previous studies.

Fluzone® High-Dose vaccine was licensed in the United States by the FDA in December 2009 based on the vaccine's safety profile and superior immunogenicity compared to Fluzone® vaccine. Fluzone® High-Dose vaccine contains 60 mcg of hemagglutinin antigen per strain of influenza virus in the vaccine as compared to 15 mcg of influenza virus hemagglutinin antigen per strain of influenza virus in standard dose Fluzone® vaccine. Fluzone® High-Dose vaccine was licensed by the FDA under an accelerated approval process to address the medical need in older adults. As a requirement of the accelerated approval pathway, Sanofi Pasteur embarked on this large-scale, two-season, confirmatory efficacy trial, involving more than 30,000 participants 65 years of age and older, to evaluate the clinical benefit of Fluzone® High-Dose vaccine compared to Fluzone® vaccine in the prevention of influenza disease.