FYI.
Personally, I'd settle for a DTaP-IPV combination.
---Len Leshin
FDA Advisory Panel Urges Agency Not to Approve
GlaxoSmithKline Vaccine
BETHESDA, MD (Reuters Health) Mar 07 - A closely divided advisory panel to
the US Food and Drug Administration 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 DTPa-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 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 [pneumococcal vaccine] Prevnar...makes me a little uncomfortable,"
said Pamela S. Diaz, medical director of communicable diseases at the
Chicago Department of Public Health.
But the biggest worries stemmed from increased rates of fever in infant
subjects 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 afebrile seizures in treatment subjects and none in controls,
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 subjects were Caucasian.
Those numbers had some experts questioning how the vaccine would function
in a more genetically diverse US population.
"You have to have at least 3,000 more US children in your database to prove
that you have safety and efficacy," said panelist Barbara Fisher, an
activist and co-founder of the National Vaccine Information Center.