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Meningococcal vaccine gets advisory panel nod.

BETHESDA, MD. -- A new conjugate meningococcal vaccine was unanimously endorsed at a joint meeting of the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee.

If approved by the FDA as expected, Aventis' Menactra would be licensed for the prevention of meningococcal serogroups A, C, Y, and W-135 in people aged 11-55 years.

The currently licensed polysaccharide meningococcal vaccine (Menomune) is indicated for travelers, occupational exposure, college students living in dormitories, immunocompromised individuals, and military recruits. Menactra offers several potential advantages over Menomune, including immune memory, a better booster effect, reduction of carriage, and herd immunity, said Dr. Luc Kuykens, vice president of regulatory affairs for Aventis Pasteur Inc., part of the sanofi-aventis group, which makes both vaccines.

Dr. Michael Decker, vice president of scientific and medical affairs at Aventis, presented the immunogenicity data that were submitted to the FDA to fulfill the requirement that Menactra be shown to be "noninferior" to Menomune.

In one of the trials, 440 healthy adolescents aged 11-18 years were given one intramuscular dose of Menactra, while 441 were given one subcutaneous dose of Menomune. The proportion achieving a fourfold rise in antibody titer ranged from 82% against serogroup Y to 97% for serogroup W-135 with Menactra, compared with 80%-95% with Menomune. Geometric mean titers at 28 days were also in the disease-protective range for both vaccines, he reported.

Similar efficacy results were seen among 2,554 healthy adults aged 18-55, of whom 1,384 received Menactra and 1,170 received Menomune. Here, fourfold rises in antibody titers were slightly lower, ranging from 89% against serogroup W-135 to 74% against serogroup Y with Menactra, compared with 94%-79% for Menomune. In all cases, "noninferiority criteria were met," he said.

In a separate evaluation of 241 healthy subjects aged 14-21, a booster dose of Menactra was given to 76 participants who had received Menactra 3 years earlier and to another group of 77 subjects who had initially received Menomune. Significantly greater antibody persistence was seen with those who initially got Menactra for serogroups A and W-135, while the difference was of borderline significance for serogroups C and Y.

Compared with a group of 88 age-matched participants who did not receive a primary dose of either vaccine, those who had been "primed" with Menactra had significantly greater geometric mean titers after the 3-year Menactra booster for all serogroups except A, in which the two groups were equal.

The findings show a "rapid, high, amnestic response, far exceeding the response of naive controls, demonstrating a rapid increase in bactericidal antibody to levels exceeding those that would be expected if reimmunized with Menomune," Dr. Decker said.

Another trial investigated the likely clinical scenario of concurrent administration of Menactra and tetanus-diphtheria vaccine. A total of 509 11-to 17-year-olds were given Menactra plus Td followed 28 days later by placebo, while another 512 were given Td plus placebo, followed 28 days later by Menactra. At 28 days' post-Menactra, geometric mean antibody responses to all four meningococcal serogroups and to tetanus were identical, while the diphtheria antibody response was twofold greater when the two vaccines were given together than when Td was given alone, Dr. Decker noted.

In adults, a likely traveler/military scenario was studied by comparing antibody responses of 469 healthy 18- to 55-year-olds given Menactra plus Typhim Vi followed 28 days later by placebo to those of 476 given Typhim Vi plus placebo followed 28 days later by Menactra. Again, responses to all four meningococcal serogroups and to Typhim Vi were similar, he said.

Safety data, presented by Aventis' Senior Director of Regulatory Affairs Dr. Gary Chikami, demonstrated higher reaction rates with Menactra than with Menomune--which is typical of conjugate vaccines--but comparable safety profiles with regard to severe solicited systemic reactions (reactions that subjects were asked to report).

The most common side effects were headache (36% Menactra vs. 29% Menomune), fatigue (30% Menactra vs. 25% Menomune) and malaise (22% vs. 17%). Most were classified as mild.

Severe solicited reactions occurred in 4.3% following Menactra and in 2.6% with Menomune. Of those, rash, headache, fatigue, malaise, and arthralgia were all significantly higher with Menactra, but the total numbers were small and the mean duration was just 1 day, he noted.

Similar safety results were seen in another adolescent trial involving 439 Menactra and 441 Menomune recipients (any systemic reaction: 57% Menactra vs. 52% Menomune, any severe systemic reaction: 3.9% vs. 4.1%), and in an adult trial of 1,371 Menactra and 1,159 Menomune recipients (any systemic reaction: 62% Menactra vs. 60% Menomune, any severe systemic reaction: 3.8% vs. 2.6%). In adults, the rate of chills was the only severe reaction that differed significantly, 0.6% with Menactra vs. 0 with Menomune.

Pain at the injection site was more frequent with Menactra than with Menomune in all age groups, ranging from 29% to 30% with Menomune and from 53% to 69% with Menactra for the adolescents and from 20% to 48% with Menomune and from 39% to 54% with Menactra among the adults. Severe injection pain occurred in less than 2% overall.

In the concurrent immunization trials, local reactogenicity of Menactra was higher than for Menomune but comparable with that of Td vaccine. There were no significant differences between the two vaccines in the rates of unsolicited events in any age group, and none were considered vaccine related, Dr. Chikami said.

Although the panel voted unanimously to support both the efficacy and safety of the vaccine, several members requested that the company gather more postlicensure antibody data to help determine exactly when boosters would be needed. Members also requested disease surveillance to determine the vaccine's impact, ongoing safety monitoring to look for rare reactions, and more data on concurrent administration of Menactra with other routine vaccines in both children and adults.

Ultimately, Aventis plans to replace Menomune with Menactra. The company is currently conducting trials in younger children and older adults with the aim of eventually seeking supplemental licenses. The price of Menactra is expected to be comparable with that of Menomune, company spokesman Len Lavenda told this newspaper.
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Title Annotation:Infectious Diseases
Author:Tucker, Miriam E.
Publication:Family Practice News
Geographic Code:1USA
Date:Oct 15, 2004
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