Thursday, November 19, 2009

FDA Panel Recommends Prevnar 13 Vaccine for Approval

From Medscape Medical News

Fran Lowry

November 19, 2009 — The US Food and Drug Administration (FDA) advisory committee on vaccines and related biological products has given a near-unanimous endorsement of the pneumococcal vaccine Prevnar 13, saying it believes the new vaccine is effective and safe for the active immunization of children against serious systemic infection with Streptococcus pneumoniae.

Ten panel members voted yes, 1 voted no, and 1 abstained when asked whether the available data presented by Pfizer, the vaccine's sponsor, were adequate to support the effectiveness of Prevnar 13 when administered to infants and toddlers at ages 2, 4, 6, and 12 to 15 months to prevent invasive pneumococcal disease caused by serotypes in the vaccine.

The vaccine is to be given in 4 doses as an intramuscular injection.

Panel member Pamela McInnes, DDS, from the National Institute of Dental and Craniofacial Research, the National Institutes of Health, Bethesda, Maryland, said she thought the data that Pfizer presented were very convincing about the vaccine's efficacy. "I think we have to look at what I think are quite compelling data in terms of functional antibodies. I am very persuaded by that."

The panel also gave a near-unanimous thumbs up to the FDA's second question about whether they thought the evidence for the vaccine's safety was adequate.

However, Patricia Ferrieri, MD, professor of pediatrics and infectious diseases at the University of Minnesota Medical Center in Minneapolis, reminded the panel that they were inferring safety about Prevnar 13 from their experience with Prevnar 7. "I just want that on the record," she said.

The panel member who voted no, Vicky Debold, PhD, director of patient safety at the National Vaccine Information Center in Vienna, Virginia, and the consumer representative on the panel, said she was not convinced about the new vaccine's safety.

"I am concerned that we are discussing whether safety has been demonstrated here, when in fact the safety data are not complete. We're not looking at the full complement of data, and it is disconcerting to me to see that, as the number of doses increase, we were seeing an increase in the severity and frequency of adverse reactions," she said.

Prevnar 13 is composed of capsular polysaccharides derived from the 7 pneumococcal serotypes contained in Prevnar 7 (4, 6B, 9V, 14, 18C, 19F, and 23F) and from 6 additional pneumococcal serotypes (1, 3, 5, gA, 7F, and 19A).

Each capsular polysaccharide is individually conjugated to diphtheria CRM197 protein, and this prompted 1 panel member to ask about the potential for hyperimmunization.

Robert Munford, MD, from the National Institutes of Health, commented that today's children may be getting hyperimmunized with diphtheria toxin. "These kids are getting so much of this, and Prevnar 13 has twice the dose of CRM. Hyperimmunization can lead to autoimmune phenomena. Is the company planning to watch for such events in its postmarketing surveillance?"

The sponsor said that the company was planning to look for autoimmune diseases in its postmarketing surveillance.

The committee was also asked to discuss — but not to vote on — whether the data presented by the sponsor supported the effectiveness of Prevnar 13 for the prevention of otitis media. Despite arguments by Wyeth that the effect of its predecessor, Prevnar 7, was substantial, some panel members were not convinced.

"This is where I get mired," said Jose Romero, MD, professor of pediatrics at University of Arkansas, Little Rock. "There is no real correlate with protection for otitis media. You can't really extrapolate from the data you have given that you get a good antibody response that would predict that you're not going to have otitis media if you get this vaccine. This is more of a black-box issue."

Pablo Sanchez, MD, from the University of Texas Southwestern Medical Center in Dallas, agreed. "We are being asked to say that this vaccine is efficacious for otitis media based on other data, and we have to extrapolate here. I would like to see more data on this."

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