SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Nov. 16 supported expanding the approval of the pneumococcal 13-valent conjugate vaccine approved in 2010 for infants and children for use in adults aged 50 and older, based on studies using surrogate end points of effectiveness.
The FDA’s Vaccines and Related Biological Products Advisory Committee voted 14 to 1 that the immunogenicity data on the vaccine, marketed as Prevnar 13 by Wyeth Pharmaceuticals Inc., supported its effectiveness in preventing pneumococcal disease caused by the serotypes contained in the vaccine in people aged 50 and older. The panel also voted 14 to 1 that the available data supported its safety in this older age group, with the panel’s consumer representative casting the no vote on both questions.
Prevnar 13 is under FDA review as an accelerated approval, which applies to products that "provide meaningful clinical benefit" over existing treatments for serious and life-threatening illnesses, which in the case of this vaccine is the protection of adults and the elderly from nonbacteremic pneumococcal pneumonia and protection from invasive pneumococcal disease, according to the FDA. A product can be approved under the accelerated approval regulation based on studies using surrogate effectiveness end points, if a follow-up clinical study confirming the benefits is conducted. If that study is negative, the FDA can withdraw approval.
The proposed adult indication for Prevnar 13 is for the prevention of pneumococcal disease (including pneumonia and invasive disease) caused by the Streptococcus pneumoniae serotypes contained in the vaccine, in adults aged 50 years and older. Prevnar 13 was recently approved for this indication in 29 countries in Europe and 8 other countries.
The vaccine was approved in 2010 for preventing invasive disease caused by the S. pneumoniae serotypes in the vaccine in children aged 6 weeks through 5 years; it is also approved for preventing otitis media caused by seven serotypes.
The adult formulation is identical to the pediatric vaccine.
In the two pivotal trials, immune responses with a single dose of Prevnar 13 were considered noninferior to the responses seen with a single dose of Pneumovax 23, a 23-valent polysaccharide vaccine approved in 1983 for immunizing adults aged 50 and older and children aged 2 years and older, who are at an increased risk for pneumococcal disease. With one exception, Pneumovax 23 contains the serotypes included in Prevnar 13 plus 11 others; it is the only adult pneumococcal vaccine approved in the United States. One study was conducted in the United States and compared Prevnar13 to Pneumovax 23. The study comprised 1,235 adults aged 50-64 years, who had not received a pneumococcal vaccine before; the other compared the two vaccines in 936 patients, aged 70 years and older, in the United States and Sweden. Those participants received Pneumovax 23 at least 5 years earlier.
For most serotypes in the vaccine, the immune responses were significantly higher with Prevnar 13 than with Pneumovax 23 among those aged 50-65 who had not received the pneumococcal vaccine previously and among those aged 70 years and older who had been previously vaccinated, according to Pfizer presentations at the meeting. (Wyeth is a wholly owned subsidiary of Pfizer Inc.)
There were no imbalances in deaths or serious adverse events among those who received Prevnar 13 and among those who received the older vaccine, but the safety database was not large enough to identify rare side effects, according to the FDA.
To confirm the results of these studies, Wyeth is conducting a placebo-controlled study of more than 85,000 adults aged 65 years and older in the Netherlands, evaluating the efficacy of the vaccine in preventing the first episode of pneumococcal pneumonia, which is underway."
The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.