By Todd Zwillich

BETHESDA, Md., Mar 08 (Reuters Health) - A closely divided advisory panel to the US Food and Drug Administration (FDA) voted on Wednesday that the agency should not approve GlaxoSmithKline's Infanrix DTaP-Hepatitis B-IPV combination vaccine for infants. Six members of the Vaccines and Related Biological Products Advisory Committee voted no, five voted yes and one abstained.

Several members claimed to be "on the fence" about whether the need for this five-in-one vaccine, which is manufactured by SmithKline Beecham Biologicals, was strong enough to override what they perceived as gaps in the company's data.

"In my gut I think that this vaccine is probably fine," Judith D. Goldberg, director of the division of biostatistics at New York University School of Medicine, said at the hearing. "I think this is a good vaccine, but I'm not totally convinced, and I'm not totally comfortable."

GlaxoSmithKline spokeswoman Carmel Hogan said in an interview that the company remains confident about the safety and efficacy of its combination vaccine, though she would not comment on whether the company plans further trials to appease the advisory panel.

"Further discussion needs to take place with the FDA," she said.

Infanrix DTaP-HepB-IPV combines four already approved infant vaccines with an as-yet unlicensed formulation of inactivated polio vaccine. Availability of the combination would have cut from 20 to 9 the number of injections infants need in order to be up-to-date with their immunizations in the first 18 months of life.

Public health experts place a premium on simplifying the complicated vaccination schedule as a way to make full immunization easier for parents and infants.

But several panelists felt that the sponsor's studies--containing more than 7,000 patients in the United States and Germany--were too small to conclusively support results suggesting that giving the 5-vaccine combination was just as effective at eliciting an immune response as giving its components separately. Experts were also troubled because pivotal trials did not look at how the combination's overall immunogenicity might be affected by other vaccines on the schedule.

"The lack of any knowledge about how this vaccine will behave when given with (the pneumococcal vaccine) Prevnar...makes me a little uncomfortable," said Pamela S. Diaz, medical director of communicable diseases at the Chicago Department of Public Health.

The biggest worries stemmed from increased rates of fever in infant study participants who had received the 5-combination vaccine. In the company's largest trial, 43% of infants who received the combination vaccine developed fever within 4 days compared with 26% of infants who received sequential vaccinations.

"We are collectively concerned about the differential rates of fever," said Dr. Robert S. Daum, a University of Chicago professor of pediatrics and acting chair of the committee.

GlaxoSmithKline also reported seven cases of dangerous seizures unrelated to fever in treated study participants and none in those who did not receive the combined vaccine, though the difference was not statistically significant.

"The pediatrician has to be convinced that this is a safe vaccine and I don't think that we have those data right now," said Dr. Walter L. Faggett, a Washington, DC pediatrician.

In the end, several panelists had asked the company to submit a new efficacy and safety trial with larger numbers and a greater ethnic diversity of patients. The largest trial in the company's series was performed in Germany, where more than 96% of the participants were white. Those numbers had some experts questioning how the vaccine would function in a more ethnically diverse US population.

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