Sanofi Pasteur announces publication of positive data for Fluzone® high-dose vaccine in The New England Journal of Medicine

Sanofi Pasteur, the vaccines division of Sanofi (EURONEXT: SAN and NYSE: SNY), today 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 (Influenza Vaccine) was more efficacious in preventing influenza (“the flu”) 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.

Fluzone High-Dose vaccine is an inactivated influenza vaccine that contains four times the amount of antigen than is contained in standard-dose Fluzone vaccine and induces a higher antibody response.
“We are thrilled that the results of this trial have shown that Fluzone High-Dose vaccine is significantly more effective than standard-dose Fluzone vaccine in providing protection against influenza in the 65 and over population,” said David P. Greenberg, M.D., Vice President, Scientific & Medical Affairs, and Chief Medical Officer, Sanofi Pasteur US. “Fluzone High-Dose vaccine is the only influenza vaccine in the US that is designed specifically to address the age-related decline of the immune system in older adults.”

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.

“Eighty-six percent of older adults have one or more chronic conditions, such as, cardiovascular disease and respiratory illnesses that can be exacerbated by influenza,” i said Keipp Talbot, MD, MPH, Assistant Professor of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tenn. and coordinating investigator of the trial. “Considering the burden of influenza in older adults, it is encouraging to see that this trial demonstrated the ability of Fluzone High-Dose vaccine to provide better protection in this high-risk population.”

The full results from this trial formed the basis for a regulatory submission to the U.S. Food and Drug Administration (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.

“Adults age 65 years and older typically account for more than half of influenza-related hospitalizations and about 90 percent of influenza-related deaths,” said John Shiver, Senior Vice President, Research and Development, Sanofi Pasteur. “We are fully committed to helping to offer protection against influenza by delivering a more effective vaccine option designed specifically to address the needs of people aged 65 years and older.”

Influenza is a serious illness impacting up to 20 percent of Americans each year, translating to approximately 15 to 60 million cases annually.ii Adults 65 years of age and older remain at high risk for influenza, despite high vaccination rates.iii,iv People aged 65 years and older do not respond to standard-dose influenza vaccine as well as younger adults and may be left without sufficient protectionv especially against influenza A/H3N2, which is considered the most burdensome in older adults.vi,vii

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. Immunogenicity (the ability of a vaccine to trigger the body to produce antibodies against an infectious agent) is commonly used to evaluate vaccines in clinical trials. Fluzone High-Dose vaccine contains 60 μg 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.

In response to the unmet medical need in older adults, Fluzone High-Dose vaccine was licensed by the FDA under the agency’s accelerated approval process. 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 standard-dose Fluzone vaccine in the prevention of influenza disease.