January 31, 2012 — The US Food and Drug Administration (FDA) Pediatric Advisory Committee today reviewed safety data on pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein), or PCV13 (Prevnar 13, Wyeth Pharmaceuticals, Inc). The panel agreed that the estimates of febrile seizure risk need to be further refined but that routine monitoring of the vaccine should continue.
The 2-day committee meeting was held in Gaithersburg, Maryland, yesterday and today.
Tina Khoie, MD, MPH, a medical officer with the Division of Vaccines and Related Product Applications Office of Vaccines Research and Review, Center for Biologics Evaluation and Research (CBER), FDA, presented an overview of the prelicensure safety data for PCV13.
PCV13 was licensed on February 24, 2010, for use in children aged 6 weeks through 5 years of age and is indicated for active immunization for the prevention of invasive disease and otitis media caused by strains of Streptococcus pneumoniae.
Use of PCV13 in the United States followed that of PCV7, which was licensed in February 2000 for children aged 6 weeks to 9 years. Only PCV13 is now distributed in the United States, and more than 21 million doses have been distributed thus far.
Compared with PCV7, PCV13 contains 6 additional pneumococcal serotypes. Both products contain aluminum phosphate adjuvant and similar emulsifiers.
Thirteen clinical trials comparing PCV7 (n = 2760) with PCV13 (n = 4729) were conducted worldwide and were included in the prelicensure safety database.
Four of the 7489 children died (3 who received PCV13 and 1 who received PCV7); all deaths were considered related to sudden infant death syndrome (SIDS), with a rate consistent with background rates.
"Serious adverse events from dose 1 through the post-infant series was reported in 3.7% of participants receiving PCV13 compared with 3.5% of those receiving PCV7," Dr. Khoie noted during her presentation.
The most frequently reported serious adverse events were wheezing pneumonia and gastroenteritis. "Rates were similar between the 2 study groups…and there were also no new or unexpected adverse events when comparing" the 2 groups, she said.
Since licensure of PCV13, hypotonic hyporesponsive episode was added to the label after 4 cases were identified in a clinical trial. The absolute rate was low for both vaccines: 0.015% with PCV13 and 0.071% with PCV7.
Two postmarketing safety studies are underway for PCV13, said Dr. Khoie. Results of the first study are expected March 30, 2012, and will evaluate the immunogenicity and safety of PCV13 in about 600 children aged 5 to 17 years. The second will involve a cohort of at least 43,000 children receiving 3 doses of PCV13 during routine medical care. Results are expected at the end of September 2014.
During her presentation, Marthe Bryant, MD, medical officer, Division of Epidemiology, Office of Biostatistics and Epidemiology, CBER, FDA, discussed currently available data from the second postmarketing safety study.
Important adverse events reported to the FDA's Vaccine Adverse Event Reporting System (VAERS) from February 24, 2010, to February 24, 2011, included 31 deaths, of which 14 were due to SIDS.
"Overall, these are similar to other SIDS reports in VAERS and do not raise any specific concern with PCV13," Dr. Bryant said.
Of 214 nonfatal serious events, intussusception (n = 43), afebrile seizure (n = 31), and febrile seizure (n = 25) were the most common. "None of these events generated a specific safety concern," she said.
However, Dr. Bryant did point out a potential increase in risk for febrile seizure with PCV13 after use of Fluzone (sanofi pasteur) in children aged 6 to 59 months. Fluzone is the only trivalent inactivated influenza (TIV) vaccine given to children aged 6 months to 4 years and was given concomitantly with PCV13 for the first time in the 2010-2011 flu season.
"The risk [for febrile seizure] was highest after concomitant vaccination with TIV and PCV13 vaccination in children 12 to 23 months," Dr. Bryant said. As a result, the FDA posted an update about this issue on January 20, 2011.
"The FDA recommends a further refinement of the estimate of febrile seizure," she said. In addition, the FDA recommends a review of data from the postmarketing survey study and continuation of routine monitoring for new safety signals.
All panel members concurred with the FDA recommendations, and no comments or concerns were raised.
Today’s session followed yesterday’s review of several pediatric drugs, including quetiapine fumarate (Seroquel, AstraZeneca), omalizumab (Xolair, Genentech/Novartis), levonorgestrel (Plan B One-Step, Teva Women's Health, Inc), and the attention-deficit hyperactivity disorder drugs dexmethylphenidate hydrochloride (Focalin and Focalin XR, Novartis) and (Daytrana, Noven Therapeutics, LLC).
Today's meeting also reviewed safety and efficacy data for GlaxoSmithKline's Cervarix (human papillomavirus bivalent [types 16 and 18] recombinant vaccine).
The FDA usually follows the advice of advisory panels but not always.
Pediatric Advisory Committee Meeting. Presented January 30-31, 2012.
The 2-day committee meeting was held in Gaithersburg, Maryland, yesterday and today.
Tina Khoie, MD, MPH, a medical officer with the Division of Vaccines and Related Product Applications Office of Vaccines Research and Review, Center for Biologics Evaluation and Research (CBER), FDA, presented an overview of the prelicensure safety data for PCV13.
PCV13 was licensed on February 24, 2010, for use in children aged 6 weeks through 5 years of age and is indicated for active immunization for the prevention of invasive disease and otitis media caused by strains of Streptococcus pneumoniae.
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Prevnar 13
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Use of PCV13 in the United States followed that of PCV7, which was licensed in February 2000 for children aged 6 weeks to 9 years. Only PCV13 is now distributed in the United States, and more than 21 million doses have been distributed thus far.
Compared with PCV7, PCV13 contains 6 additional pneumococcal serotypes. Both products contain aluminum phosphate adjuvant and similar emulsifiers.
Thirteen clinical trials comparing PCV7 (n = 2760) with PCV13 (n = 4729) were conducted worldwide and were included in the prelicensure safety database.
Four of the 7489 children died (3 who received PCV13 and 1 who received PCV7); all deaths were considered related to sudden infant death syndrome (SIDS), with a rate consistent with background rates.
"Serious adverse events from dose 1 through the post-infant series was reported in 3.7% of participants receiving PCV13 compared with 3.5% of those receiving PCV7," Dr. Khoie noted during her presentation.
The most frequently reported serious adverse events were wheezing pneumonia and gastroenteritis. "Rates were similar between the 2 study groups…and there were also no new or unexpected adverse events when comparing" the 2 groups, she said.
Since licensure of PCV13, hypotonic hyporesponsive episode was added to the label after 4 cases were identified in a clinical trial. The absolute rate was low for both vaccines: 0.015% with PCV13 and 0.071% with PCV7.
Two postmarketing safety studies are underway for PCV13, said Dr. Khoie. Results of the first study are expected March 30, 2012, and will evaluate the immunogenicity and safety of PCV13 in about 600 children aged 5 to 17 years. The second will involve a cohort of at least 43,000 children receiving 3 doses of PCV13 during routine medical care. Results are expected at the end of September 2014.
During her presentation, Marthe Bryant, MD, medical officer, Division of Epidemiology, Office of Biostatistics and Epidemiology, CBER, FDA, discussed currently available data from the second postmarketing safety study.
Important adverse events reported to the FDA's Vaccine Adverse Event Reporting System (VAERS) from February 24, 2010, to February 24, 2011, included 31 deaths, of which 14 were due to SIDS.
"Overall, these are similar to other SIDS reports in VAERS and do not raise any specific concern with PCV13," Dr. Bryant said.
Of 214 nonfatal serious events, intussusception (n = 43), afebrile seizure (n = 31), and febrile seizure (n = 25) were the most common. "None of these events generated a specific safety concern," she said.
However, Dr. Bryant did point out a potential increase in risk for febrile seizure with PCV13 after use of Fluzone (sanofi pasteur) in children aged 6 to 59 months. Fluzone is the only trivalent inactivated influenza (TIV) vaccine given to children aged 6 months to 4 years and was given concomitantly with PCV13 for the first time in the 2010-2011 flu season.
"The risk [for febrile seizure] was highest after concomitant vaccination with TIV and PCV13 vaccination in children 12 to 23 months," Dr. Bryant said. As a result, the FDA posted an update about this issue on January 20, 2011.
"The FDA recommends a further refinement of the estimate of febrile seizure," she said. In addition, the FDA recommends a review of data from the postmarketing survey study and continuation of routine monitoring for new safety signals.
All panel members concurred with the FDA recommendations, and no comments or concerns were raised.
Today’s session followed yesterday’s review of several pediatric drugs, including quetiapine fumarate (Seroquel, AstraZeneca), omalizumab (Xolair, Genentech/Novartis), levonorgestrel (Plan B One-Step, Teva Women's Health, Inc), and the attention-deficit hyperactivity disorder drugs dexmethylphenidate hydrochloride (Focalin and Focalin XR, Novartis) and (Daytrana, Noven Therapeutics, LLC).
Today's meeting also reviewed safety and efficacy data for GlaxoSmithKline's Cervarix (human papillomavirus bivalent [types 16 and 18] recombinant vaccine).
The FDA usually follows the advice of advisory panels but not always.
Pediatric Advisory Committee Meeting. Presented January 30-31, 2012.
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