FDA licenses high-dose flu vaccine for elderly

Dec 28, 2009 (CIDRAP News) – The US Food and Drug Administration (FDA) has approved a high-dose seasonal influenza vaccine for elderly people, whose aging immune systems may not respond effectively to flu vaccines intended for younger people.

The vaccine, Fluzone High-Dose, made by Sanofi Pasteur, contains four times as much antigen (active ingredient) as standard seasonal flu vaccines. The FDA and the company announced its approval Dec 23.

The vaccine is intended for people aged 65 years and older and will be available in time for the 2010-11 flu season, Sanofi officials said in a press release. It apparently is the first flu vaccine licensed in the United States specifically for older people.

In a large phase 3 trial conducted during the 2006-07 flu season, the vaccine induced significantly stronger immune responses than standard-dose vaccine did. Nonserious side effects were more common with the high-dose vaccine, but the overall safety profile was similar to that of the standard vaccine, the company said. The study did not assess actual protection from flu.

The FDA used its "accelerated approval pathway" to review the vaccine, the company having filed its application in March, according to Michelle Yeboah, an FDA spokeswoman. As part of that process, Sanofi will be required to conduct further studies to determine whether the vaccine decreases flu in recipients, the agency said.

"As people grow older, their immune systems typically become weaker," said Karen Midthun, MD, acting director of the FDA's Center for Biologics Evaluation and Research, in the FDA announcement. "This is the first vaccine that uses a higher dose to induce a stronger immune response that is intended to better protect the elderly against seasonal influenza."

Researchers estimate that elderly people account for about 90% of the deaths related to seasonal flu each year. In contrast, younger and middle-aged adults bear most of the burden of severe cases and deaths related to the pandemic H1N1 virus.

Each dose of Fluzone High-Dose will contain 180 micrograms (mcg) of antigen—60 mcg for each of the three flu strains normally targeted in seasonal vaccines, the FDA said. Standard seasonal flu vaccines contain 15 mcg for each strain, for a total of 45 mcg.

Sanofi Pasteur has been the largest producer of flu vaccine for the US market in recent years. Ellyn Schindler, a company spokeswoman, declined to say today how many doses of the high-dose vaccine might be made for the next season, commenting that production plans are proprietary and will depend in part on customer reservations.

"We have two influenza vaccine production facilities licensed in the U.S. which should provide adequate capacity to produce this vaccine as well as our other formulations of influenza vaccines for the 2010-2011 season," Schindler said.

Sanofi made 50.5 million seasonal vaccine doses this year and is producing 75.3 million doses of pandemic H1N1 vaccine, she noted.

The phase 3 trial of Fluzone High-Dose involved 3,856 elderly people, about two thirds of whom received that vaccine and a third the standard dose of Fluzone, according to Sanofi. A report of the trial was published in the Journal of Infectious Diseases (JID) in July.

Volunteers who received the high-dose vaccine had significantly stronger immune responses than those who received the standard dose. The response to the two influenza A strains (H3N2 and H1N1) in the vaccine met predefined superiority criteria, while the response to the B strain met noninferiority criteria, according to the JID report.

Injection-site reactions were more common in those who received the high-dose vaccine, but they were mild to moderate, the report said. The FDA said the rates of serious adverse events were comparable for the two vaccines.

In an editorial that accompanied the JID report, vaccine experts Gregory A. Poland of the Mayo Clinic and Mark J. Mulligan of Emory University commented, "Overall, the rate of adverse events in the HD [high-dose] vaccine group was acceptable although somewhat increased, as would be anticipated" for high-dose trivalent influenza vaccine (TIV).

Multiple studies now have yielded "uniform evidence of enhanced immunogenicity, acceptable reactogenicity, safety, and some evidence of efficacy for HD TIV influenza vaccines," Poland and Mulligan wrote.

See also:

Dec 23 Sanofi Pasteur news release
http://www.sanofipasteur.us/sanofi-pasteur2/sp-media/SP_US/EN/54/1041/MKT%2018870%20FDA%20Licensure%20of%20Fluzone%20High-Dose%20Vaccine%20FINAL%2012-23-09-GLOBAL.pdf

Dec 23 FDA release
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm195483.htm

Vaccine fact sheet
http://multivu.prnewswire.com/mnr/sanofipasteur/41724/docs/41724-FluzoneHighDoseFactSheet.pdf

Jul 15 JID study abstract
http://www.journals.uchicago.edu/doi/abs/10.1086/599790

Jul 15 JID editorial
http://www.journals.uchicago.edu/doi/pdf/10.1086/599791

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