ATLANTA — Wyeth Pharmaceuticals is in the process of planning the transition from routine childhood immunization with the 7-valent Prevnar to use of a 13-valent pneumococcal conjugate vaccine that is still under investigation.
The Food and Drug Administration has granted fast-track status for PCV13 for the pediatric indication, based on “an unmet medical need.” The company plans to complete the data submission process for PCV13 by the end of this month, at which point the agency will decide about priority review, Peter Paradiso, Ph.D., vice president of new business and scientific affairs at Wyeth Pharmaceuticals, Collegeville, Pa., said at the winter meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.
“Our goal is that PCV13 will replace PCV7,” he said.
The 13-valent version contains the same amounts of the same seven serotypes that Prevnar has (4, 6B, 9V, 14, 18C, 19F, and 23F) along with six new strains (1, 3, 5, 6A, 7F, and 19A). Each of these polysaccharides in both vaccines is conjugated to the same carrier protein, CRM197, using the same conjugation chemistry. “So, PCV13 uses a technology that has worked successfully with Prevnar,” he noted.
Since the introduction of Prevnar in 2000, the proportion of cases of invasive pneumococcal disease (IPD) caused by the seven vaccine strains has declined dramatically, while the proportion due to other strains—19A in particular—has risen. In 2006, the proportion of IPD cases caused by the seven strains included in Prevnar was 2% in children aged younger than 2 years and 4% in those aged 2-4 years. In contrast, the proportion of IPD cases caused by the 13 serotypes in the new version was 64% and 73%, respectively, with half of the cases due to 19A.
“So, PCV13 uses a technology that has worked successfully with Prevnar,” Peter Paradiso, Ph.D., of Wyeth Pharmaceuticals, said. ©Parker Clayton Smith
Dr. Paradiso summarized previously reported data from a pivotal trial done in Germany in which 603 infants were randomized to receive either PCV7 or PCV13 at 2, 3, and 4 months of age. The 13-valent version was noninferior against each serotype, while provoking a high antibody response rate to each of the six new serotypes. The overall safety profile of PCV13 was comparable with that of PCV7 in a database that includes 4,783 PCV13 recipients in a total study population of 7,240, he said.
Wyeth's transition scheme—which would be subject to approval by both the FDA and the ACIP after PCV13 is licensed—would involve the substitution of PCV13 for PCV7 at any point in the immunization schedule.
Because data have shown that a single dose of PCV13 will induce an immune response to the six new serotypes in more than 90% of children aged 12 months and older, any child who received the primary three-dose series with PCV7 could simply receive PCV13 as a booster after they reach the age of 12 months. For children 12 months and older who already received the complete series with PCV7 including the booster, one additional dose of PCV13 would be needed for protection against the six new strains. Infants aged 6 months or younger who received one or two doses of PCV7 would complete the primary series and the booster using PCV13.
In January, Wyeth initiated a study in the Yukon-Kuskokwim Delta region of Alaska to test the safety and effectiveness of this scheme in children younger than 5 years old, he said.
The company will first seek an indication for the use of PCV13 in children younger than 5 years old. After that, it hopes to bring it to adults over age 50, and ultimately to the entire population. “Our goal is to fill in the gaps and make this vaccine available for all age groups,” Dr. Paradiso said.
In response to an audience member's query as to whether PCV13 would cost more than PCV7, Dr. Paradiso replied, “I honestly don't know the answer to that question. Obviously, that's something you'll hear about as we get closer [to implementation].