GlaxoSmithKline will update Pediarix labeling to include more information about co-administration with Wyeth's Prevnar before the end of the 2003.

The labeling update could further simplify the pediatric immunization schedule. Pediarix combines the current DTaP, IPV and hepatitis B vaccines into a single shot. Labeling states that it can be co-administered with haemophilus influenza b conjugate vaccine based on safety and immunogenicity data from clinical trials.

If similar language is added about the pneumococcal conjugate vaccine Prevnar, the standard immunization package for children in the first year of life could be as simple as three shots (Pediarix, Hib and Prevnar) administered at two, four and six months.

FDA approved Pediarix Dec. 13 for "active immunization against diphtheria, tetanus, pertussis (whooping cough), all known subtypes of hepatitis B virus and poliomyelitis caused by poliovirus Types 1, 2, and 3" (see ¹ Also see "GSK Pediarix Price Is $82.54 Per Dose; Coverage Meeting Set For February" - Pink Sheet, 23 December, 2002.).

The expected Prevnar labeling update will be based on the final report from two Phase III studies of Pediarix co-administered with Hib and Prevnar, FDA's approval letter states. Both studies completed patient accruals in 2002 and are scheduled to finish during the first half of 2003. "Revised labeling will be submitted by Dec. 15," FDA said.

Pediarix' labeling at launch includes limited data on co-administration with Prevnar, noting that safety data has been gathered for the first dose, but not immunogenicity data.

GSK's other Phase IV commitment is a large safety surveillance trial to be conducted at an HMO. The study will "evaluate as primary endpoints the risk of seizures associated with fever and the risk of medically attended fever following Pediarix administration," the approval letter says.

Pediarix labeling includes a warning regarding fever, the most common adverse event seen in Pediarix safety studies. "Administration of Pediarix is associated with higher rates of fever relative to separately administered vaccines," the warnings section states.

"In one study that evaluated medically attended fever after the first dose of Pediarix or separately administered vaccines, infants who received Pediarix had a higher rate of medical encounters for fever within the first four days following vaccination."

FDA's Vaccines & Related Biological Products Advisory Committee expressed concern about the risk of fever and seizures at its March 2001 review of the product. The committee voted against approval at that time, primarily due to concerns that the efficacy of the combined vaccine had not been validated with sufficient U.S. immunogenicity data (² Also see "GSK Infanrix Combination Vaccine BLA Needs More U.S. Immunogenicity Data" - Pink Sheet, 12 March, 2001., p. 7).

Labeling says prevalence of fever was highest on the day of vaccination and the day after and that 98% of cases of fever resolved within four days after vaccination. The trial found that 27.9% of the 667 patients given Pediarix had fever of at least 100.4°F within four days following dosing, compared to 19.8% of the 333 patients given separate vaccines.

The rate of other adverse events with Pediarix use was comparable to that of the separately administered vaccines, labeling says. Other than fever, the most commonly observed adverse events in clinical trials were local injection site reactions such as pain, redness or swelling, and fussiness.

Labeling notes the occurrence of seizures in a German safety trial. Of 4,666 subjects administered Pediarix plus Hib, six reported seizures within the 30-day post-vaccination study period, labeling says. Two of the subjects had a febrile seizure, and one of those also developed afebrile seizures. The remaining four were afebrile seizures, including two with infantile spasms.

The Phase IV study will begin April 30 and finish in 2006, with the final clinical study report submitted to FDA by May 31, 2007, the approval letter states.

Pediarix studies compared the immunogenicity of the component antigens to those of licensed vaccines. A trial comparing Pediarix to its components showed immune response for the combination "to be non-inferior to those achieved following separately administered vaccines," labeling states, although the vaccine response for filamentous hemagglutinin "marginally exceeded the 10% limit for non-inferiority."

The Pediarix BLA was submitted July 2, 1999; FDA issued a "complete review" letter May 1, 2000.

Pediarix Simplifies Vaccine Schedule; Prevnar Labeling Update Due In 2003

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