By picking up serotype 19A, Pfizer's next-generation pneumococcal disease vaccine Prevnar 13 is armed to protect against the most prevalent strain of Streptococcus pneumoniae left in the U.S.
The boosted protection in the new vaccine won't likely do much to boost Prevnar 13's commercial viability in the U.S., since the firm's 7-valent Prevnar already dominates the market. Read on...
By picking up serotype 19A, Pfizer's next-generation pneumococcal disease vaccine Prevnar 13 is armed to protect against the most prevalent strain of Streptococcus pneumoniae left in the U.S.
The boosted protection in the new vaccine won't likely do much to boost Prevnar 13's commercial viability in the U.S., since the firm's 7-valent Prevnar already dominates the market. But it will help ensure that Pfizer, which acquired the product through its merger with Wyeth, will maintain its edge in the U.S. against growing competition from GlaxoSmithKline's 10-valent Synflorix .
FDA action on the Prevnar 13 sBLA is due Dec. 30. Approval is likely following the Vaccines and Related Biological Products Advisory Committee's 10-1 endorsement Nov. 18 of a claim that the additional six serotypes in Prevnar 13 provide added protection against invasive pneumococcal disease (IPD)
Pfizer is also proposing a claim for protection against otitis media, but since all the data for that indication would come post-market, the panel was hesitant to endorse it beyond what has been demonstrated for the 7 serotypes in Prevnar
The boosted claim against otitis media would be helpful in the U.S. - where Prevnar has successfully knocked out much of the IPD incidence but otitis media is still a problem - but would not be the main driver abroad, where the real potential for pneumococcal disease vaccines lies. Officials from the Centers for Disease Control and Prevention told the advisory committee that Prevnar 13 encompasses between 80 percent to 90 percent of the more than 14 million cases of pneumococcal disease that occur worldwide annually.
GSK is also vying for that market. Its 10-valent Synflorix got a headstart in establishing a position in Europe, where it was approved in March. European approval of Prevnar 13 should also be forthcoming, as the European Medicines Agency's Committee for Medicinal Products for Human Use gave it a positive opinion in September.
GSK has not filed Synflorix with FDA, and the firm said there is no planned timeline to do so. It's unlikely that the 10-valent Synflorix could gain much ground against the 13-valent Prevnar, which is expected to rapidly become as ubiquitous in the U.S. as its predecessor. But a chink in Prevnar 13's data - in the form of 3 serotypes in the new vaccine that came up inferior compared to those in the original Prevnar - could create a slight opening for Synflorix elsewhere.
The Case Of The Underperforming Serotypes
The case of those underperforming serotypes was posed to the advisory committee. Some panel members did initially express concern, but they ultimately voiced - and voted for - comfort that the 13-valent version is at least as good as the 7-valent version.
All new pneumococcal vaccines must prove non-inferiority to Prevnar or another conjugate with proven efficacy, since the ubiquity of Prevnar makes placebo-controlled trials unethical. Per World Health Organization recommendations, non-inferiority was measured according to comparisons of immunoglobulin (IgG) antibody response rates of ? 0.35 ug/mL after the third and fourth doses.
To calculate non-inferiority for the seven common serotypes, direct comparisons could be made. For the six new serotypes, comparisons were made to the lowest antibody response elicited by the 7-valent serotype group in Prevnar.
In the main immunogenicity study, three serotypes in Prevnar 13 failed those comparisons: non-inferiority was missed for one of the six new serotypes (serotype 3), and for two in the common 7-valent group (6B and 9V).
But the committee questioned the significance of those comparisons, pointing out that non-inferiority does not necessarily have to be met for each serotype in a new vaccine.
Pfizer Chief Scientific Officer-Vaccine Research Emilio Emini helped alleviate concern by noting that 6B and 9V missed non-inferiority only according to the formal criteria, but did pass the test in terms of overall antibody response.
Committee member Pamela McInnis, National Institutes of Health, supported that explanation. "I understand the origin of [the WHO recommendations]," she said, but "somehow, in this conversation, I think it's taking on a tone and relevance that was never intended to be, and I'm a little bothered by that."
And though serotype 3 missed non-inferiority across the board - for both primary and secondary endpoint measures - FDA pointed out that since it is a new strain not included in the 7-valent Prevnar, there was no true comparator.
McInnis said that while everyone would feel more comfortable seeing data showing high levels of all antibodies, "we have to look very seriously at what I think are quite compelling data in terms of functional antibodies. I'm very persuaded by that. ... And the activity in all of the [sero]types trends very positively, so I think that although the intention of the whole WHO conference was obviously to try to be helpful, we have to be careful about the interpretation of that intent."
Five Proposed Or Ongoing Efficacy Studies
Pfizer has proposed an extensive post-licensure study plan including a Phase IV safety study of 43,000 Prevnar-vaccinated children identified through the Northern California Kaiser Permanente medical record database.
The company is also protecting its hold on the pneumococcal vaccine market with five proposed or ongoing efficacy studies that are not required as a condition for licensure: three in IPD, and two in otitis media.
One of the IPD studies will be a case-control study that will rely on data from CDC's Active Bacterial Core Surveillance system. (FDA clarified that Pfizer will rely on CDC's data, but that CDC will not be conducting the study for the company). The study is designed to determine Prevnar 13's effectiveness on a per-serotype, per-dose basis, and will include a total database of 27 million doses over the years 2010-2013.
The other two IPD efficacy studies include an observational study of 140,000 children in the Northern California Kaiser Permanente database that will be conducted from 2010 to 2014 to determine the annual IPD incidence, and an ongoing Phase III, open-label trial in 2,500 Alaskan native children.
The firm has also proposed two effectiveness studies in otitis media: an observational otitis media and nasopharyngeal colonization effectiveness study of 350 subjects, and a surveillance study looking at otitis media doctors' office visits using the national administrative databases.
Pfizer's efforts to corner the pneumococcal disease vaccine market do not end with the six new serotypes in Prevnar 13 or the planned robust post-licensure study program. Learning from past shortages in Prevar supply, the firm has geared-up production to meet demand: company representatives to the Advisory Committee on Immunization Practices in October reported that 13 million doses of the new vaccine have already been filled and 20 million are expected by the end of the year.
And even as Pfizer prepares to launch the follow-on vaccine, the immunology community is already thinking about the next generation product.
- Jamie Hammon
