Sanofi reports trial results for novel flu vaccines

Oct 25, 2010 (CIDRAP News) – Sanofi Pasteur has reported encouraging preliminary results in clinical trials of two novel influenza vaccines—a four-strain vaccine containing two influenza B strains and an intradermal vaccine.

In a phase 3 trial, the intradermal vaccine—delivered with a shallow prick into the skin instead of a jab into muscle—induced immune responses comparable to those from a standard intramuscular vaccine and had a similar safety profile, the company said in a press release today.

Likewise, a phase 2 trial showed that the quadrivalent vaccine was "immunologically non-inferior" to a standard trivalent (three-strain) vaccine and had similar side effects, the company reported in a separate release.

Both sets of findings were announced at the Infectious Diseases Society of America's annual meeting in Vancouver, B.C., which ended yesterday.

Intradermal trial results
Intradermal flu vaccines have been discussed as a potential way to stretch vaccine supplies, because they may require less antigen, and to improve vaccine acceptance. Sanofi already has an intradermal vaccine licensed in Europe and marketed there as Intanza and IDFlu.

Sanofi applied to the Food and Drug Administration (FDA) earlier this year for approval of its Fluzone Intradermal vaccine. The company said the FDA has accepted the filing and that "an action date is anticipated in the first half of 2011."

In the phase 3 trial, the Fluzone Intradermal vaccine was compared with the standard Fluzone intramuscular vaccine. The intradermal version has 9 micrograms (mcg) of hemagglutinin for each of three flu strains, versus 15 mcg for the intramuscular formulation, the company said.

Researchers recruited 4,292 adults (ages 18 to 64) for the trial, conducted in the 2008-09 flu season. Two thirds of the participants were randomly assigned to receive Fluzone Intradermal and the rest received Fluzone.

A hemagglutination inhibition assay was used to assess antibody responses to the vaccines. The company statement did not give specific results, but said the immunologic responses to the two vaccines were similar.

"The results from this large phase III study in adults show that administration of influenza vaccine with an intradermal microinjection system may reduce the amount of antigen required for an immune response similar to that seen with Fluzone vaccine," Geoffrey J. Gorse. MD, a professor of internal medicine at St. Louis University, said in the press release.

Sanofi also said the two vaccines triggered comparable levels of side effects. Injection-site reactions were more common with the intradermal vaccine, "as was expected given that the vaccine antigens were administered into the dermal space," the statement said. Most of the reactions were of "Grade 1 or Grade 2" intensity and resolved in 3 to 7 days.

Quadrivalent vaccine findings
Standard flu vaccines now target three strains of flu: A/H1N1, A/H3N2, and B. The idea of putting two B strains into a flu vaccine was spurred by the difficulty in recent years of predicting which type B lineage, Victoria or Yamagata, will dominate in any given season, the Sanofi release noted. Experts say a vaccine targeting one lineage provides little protection against the other.

Sanofi's quadrivalent vaccine contains an antigen from each of the two B lineages, the company said. In the phase 2 trial, 570 adults were randomly assigned to receive either the 2008-09 trivalent influenza vaccine (TIV), the 2009-10 TIV, or the quadrivalent vaccine (QIV). The study took advantage of the fact that the two seasonal vaccines contained the same influenza A strains but different B lineages.

Researchers found that the hemagglutination antibody responses to the QIV (as measured by geometric mean titers, fourfold rise in titers, and the percent of volunteers with titers of at least 1:40) were comparable to those for both licensed TIVs, Sanofi reported. The quadrivalent vaccine induced "statistically non-inferior" antibody responses to each A and B strain.

The company also said the safety profiles of the quadrivalent and trivalent vaccines "did not materially differ." The most common solicited local reaction was pain, and the most common systemic reactions were myalgia, headache, and malaise.

"Based on the data from this trial, Sanofi Pasteur plans to proceed with Phase III clinical trials of Fluzone Quadrivalent vaccine this fall," said Wayne Pisano, Sanofi's president and CEO, in the release.

See also:

Oct 25 Fluzone Intradermal press release

Oct 25 Fluzone Quadrivalent press release

Jan 16, 2009, CIDRAP News story "Experts consider 4-strain flu vaccine to fight B viruses"

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