Manufacturers react cautiously to flu vaccine efficacy analysis

Oct 31, 2011 (CIDRAP News) – Companies that market influenza vaccines in the United States are reacting cautiously to last week's meta-analysis that highlighted gaps in the evidence for the efficacy of the vaccines, with officials stressing that vaccines are still the best preventive tool and that the firms are working to improve them.

The meta-analysis, published last week in The Lancet Infectious Diseases, showed that evidence from the best randomized controlled trials (RCTs) indicates that flu vaccines have an efficacy of about 59% in adults aged 18 to 65. The authors emphasized that vaccines remain the best defense against flu, but that better vaccines are needed.

The authors also found that RCTs show the nasal-spray vaccine (live attenuated influenza vaccine, or LAIV) works well in children 6 months to 7 years old, but RCT evidence of the vaccine's efficacy in older children and adults is lacking.

The investigators found just one high-quality observational study of flu vaccine effectiveness in adults 65 and older, and it showed the vaccine was 59% effective. No high-quality RCTs of vaccine in efficacy in older adults were found, but such trials have been deemed unethical because flu vaccination has been recommended for older adults since the 1960s.

Five vaccine manufacturers who were contacted by CIDRAP News said they agreed that existing vaccines should continue to be used while the quest for better ones continues, though one firm commented that the authors excluded some studies offering evidence of the benefits of flu vaccines.

A fairly typical response came from Jennifer Armstrong, a spokeswoman for GlaxoSmithKline (GSK): "Prior analyses as well as this one have shown that the existing influenza vaccines are effective in preventing influenza and its consequences. These vaccines have been determined to be cost-saving to society as a whole, and beneficial to many individuals. We at GSK, and many others, are working to make a more effective vaccine."

The most detailed comments were provided by MedImmune, maker of FluMist, the nasal spray vaccine. Chris Ambrose, MD, the company's senior director of medical affairs, said the meta-analysis "provides a valuable summary of the available data from placebo-controlled efficacy studies and observational effectiveness studies regarding the impact of influenza vaccines on culture/PCR [polymerase chain reaction]-confirmed influenza illness. It demonstrates that efficacy is well-established, high, and consistent for the LAIV in children and that efficacy is well-established for trivalent inactivated vaccines [TIV] in younger adults."

Ambrose called the analysis "well done and appropriate," adding, "The primary limitation, which is discussed by the authors, is the exclusion of high-quality randomized, controlled studies that either (1) did not include a placebo or non-influenza vaccine control or that (2) measured protection against influenza-like illness rather than culture/PCR-confirmed influenza."

For example, the analysis excluded randomized studies that directly compared LAIV and TIV in children 6 to 17 years and studies that demonstrated LAIV protection in adults against influenza-like illness, Ambrose said, adding that similar studies with TIV may have also been excluded.

The authors of the meta-analysis used strict criteria in an effort to exclude all but the most reliable studies. They did not include studies in which ILI was used as an outcome, focusing exclusively on those that used lab-confirmed flu.

Novartis officials declined to comment specifically on the meta-analysis but stressed that the company regards vaccination as the best protection against seasonal flu.

"While we are unable to comment directly on the design or outcome of this analysis, we agree with the general point of view of the authors that flu vaccination plays an important role in protecting against the flu and flu-related illness," said Elizabeth Power, spokeswoman for Novartis Vaccines and Diagnostics in Cambridge, Mass.

"As a leading influenza vaccines manufacturer and as a company actively engaged in developing the next generation of vaccines for a range of illnesses, Novartis is committed to developing new and improved influenza vaccines for those at highest risk of complications, such as young children and older adults," she said.

As an example, she cited the company's recent report of phase 3 trial results for a flu vaccine containing its MF59 adjuvant. As reported previously, the report in the New England Journal of Medicine showed that the vaccine achieved 86% efficacy in children 6 months through 5 years old, versus 43% for conventional non-adjuvanted vaccines.

An official with CSL Biotherapies praised the meta-analysis while expressing hope that the findings won't undermine confidence in the vaccine.

"The authors have written a good and rigorous paper that does support the use of current influenza vaccines while new vaccines are developed," said Darryl Maher, MD, vice president, medical and research. "It would be disappointing if those most at risk from influenza complications were to lose confidence in influenza vaccination on the basis of the paper."

Maher also commented, "It has been known for a long time that there is room for improvement in the efficacy of influenza vaccines. Industry recognizes this and continues to invest in the ongoing development of influenza vaccines resulting in advances such as adjuvanted influenza vaccines, live attenuated vaccines [which are covered in the paper] and high-dose vaccines in the elderly. There is also significant ongoing work by biopharmaceutical companies and academics to try to develop a universal influenza vaccine, but this remains extremely challenging."

Donna Cary, a spokeswoman for Sanofi Pasteur, the largest supplier of flu vaccine in the United States, said she was not sufficiently familiar with the Lancet report to comment on it specifically, but she noted that the company has been working to develop more effective flu vaccines.

As examples, she cited Fluzone High-Dose, the recently licensed high-dose vaccine designed to boost immune responses in older people, and Fluzone Intradermal, which was approved in May and is injected just under the skin surface.

See also:

Oct 25 CIDRAP News story "Strict meta-analysis raises questions about flu vaccine efficacy"

Jul 18 CIDRAP News story on 2011 flu vaccine production plans, with company projections

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