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FDA Expands Labeling for Fluzone High-Dose Vaccine for Adults 65 and Older

New data show high-dose vaccine more effective than low-dose product

The FDA has approved the supplemental biologics license application (sBLA) for Fluzone High-Dose influenza vaccine (Sanofi Pasteur) to include efficacy data in the product’s prescribing information. These data demonstrate that Fluzone High-Dose vaccine provided improved protection against influenza infection compared with standard-dose Fluzone vaccine (trivalent intramuscular formulation) in adults 65 years of age and older.

The prescribing information for Fluzone High-Dose vaccine now includes data from a large-scale efficacy and safety trial published August 14, 2014, in the New England Journal of Medicine.

The study was a double-blind, post-licensure efficacy trial conducted in the U.S. and Canada in which adults 65 years of age and older were randomly assigned to receive either Fluzone High-Dose vaccine or Fluzone vaccine. The study was conducted over two influenza seasons (2011–2012 and 2012–2013).

The trial compared the efficacy and safety profiles of Fluzone High-Dose vaccine with those of Fluzone vaccine. The analysis set for efficacy assessments included 15,892 Fluzone High-Dose vaccine recipients and 15,911 Fluzone vaccine recipients. The study’s primary endpoint was the occurrence of laboratory-confirmed influenza (as determined by culture or polymerase chain reaction) caused by any influenza viral type or subtype in association with influenza-like illness (ILI), defined as the new onset or exacerbation of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing, concurrent with at least one of the following systemic signs or symptoms: temperature greater than 99.0 degrees F (37.2 degrees C), chills, tiredness, headaches, or myalgia.

A secondary endpoint was the occurrence of culture-confirmed influenza caused by viral types or subtypes antigenically similar to those contained in the vaccines in association with a modified Centers for Disease Control and Prevention (CDC)-defined ILI, defined as the occurrence of a temperature greater than 99.0 degrees F with cough or sore throat. The efficacy rate for Fluzone High-Dose vaccine compared with Fluzone vaccine for this endpoint was 51.1%.

The safety analysis set included 15,992 Fluzone High-Dose vaccine recipients and 15,991 Fluzone recipients. Within the study surveillance period (approximately 6 to 8 months post-vaccination), 1,323 (8.3%) Fluzone High-Dose vaccine recipients and 1,442 (9.0%) Fluzone vaccine recipients experienced a serious adverse event (SAE). Within 30 days post-vaccination, 204 (1.3%) Fluzone High-Dose vaccine recipients and 200 (1.3%) Fluzone vaccine recipients experienced an SAE. Most of these participants had one or more chronic comorbid illnesses. A total of 167 deaths was reported within 6 to 8 months post-vaccination: 83 (0.5%) among Fluzone High-Dose vaccine recipients and 84 (0.5%) among Fluzone vaccine recipients; no deaths were considered by the investigators to be related to vaccination.

The study also found that Fluzone High-Dose vaccine was 24.2% more effective than standard-dose Fluzone vaccine in preventing laboratory-confirmed influenza caused by any influenza viral type or subtype in association with ILI, the primary endpoint. This suggests 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 subjects 65 years of age and older.

Fluzone High-Dose vaccine is an inactivated flu vaccine that contains four times the amount of antigen (60 mcg hemagglutinin [HA] per strain) than is contained in standard-dose Fluzone vaccine (15 mcg HA per strain). Post-vaccination, Fluzone High-Dose vaccine induces higher antibody responses compared with standard-dose Fluzone vaccine. In response to the unmet medical need in older adults, Fluzone High-Dose vaccine was licensed by the FDA in December 2009 under the agency’s accelerated approval process. Licensure was based on the vaccine’s safety profile and superior immunogenicity compared with 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.

Adults aged 65 years and older typically account for more than half (60%) of influenza-related hospitalizations and for almost all (90%) of influenza-related deaths. Studies have shown that people aged 65 years and older do not respond to standard-dose influenza vaccine as well as do younger adults and may be left without sufficient protection, especially against influenza A/H3N2, which is considered to be the most burdensome in older adults.

Sources: Sanofi Pasteur; November 3, 2014; and NEJM; August 14, 2014.

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Decision supported by data from more than 4,000 patients