VRBPAC March 15, 2005

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VRBPACMarch 15, 2005

• Theresa Finn, Ph.D
• DVRPA, OVRR, CBER

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Outline

• Introduction
• Tdap vaccines
• 1997 VRBPAC
• Licensure of pertussis vaccines for older
  individuals
• Boostrix
• Questions/Discussion

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Tdap
Tetanus Toxoid, Reduced Diphtheria Toxoid and
Acellular Pertussis Vaccine, Adsorbed Boostrix I
ndication Single booster dose individuals 10-18
years of age ADACEL Indication Single booster
dose individuals 11-64 years of age
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June 5, 1997 VRBPAC

• DTaP vaccines licensed for use in infants and
  children following clinical endpoint efficacy
  studies
• No well accepted serologic or laboratory
  correlate of clinical efficacy of pertussis
  vaccines

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VRBPAC June 5, 1997 contd

• Question 1 Can demonstration of efficacy of a
  given acellular pertussis vaccine administered as
  a primary series to infants serve as the basis
  for efficacy of that vaccine when administered as
  a booster dose to adolescents and adults?
• YES

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VRBPAC June 5, 1997 contd

• Question 2 Is demonstration of an comparable
  antibody response in adults/adolescents and
  infants an appropriate indicator that the
  different age groups respond to the vaccine in
  equivalent manners?
• i.e. Can we use antibody to bridge the 2 age
  groups and conclude efficacy in the older
  population?
• YES

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VRBPAC June 5, 1997 contd

• Adolescents and adults Clinical endpoint
  pertussis efficacy study not required for
  licensure in these age groups

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Pertussis serology bridge

• Non-inferiority of the immune response of
  adolescents/adults compared to the immune
  response of infants who received a primary series
  of the same antigens in a clinical endpoint
  efficacy study
• i.e. For each antigen
• UL 95 CI ratio GMC infants/GMC older individuals
  lt1.5
• OR
• LL 95 CI ratio GMC older individuals/GMC infants
  gt0.67

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Additional immunogenicity endpoints

• Booster response to each antigen
• 4-fold or 2-fold rise in antibody concentration

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Boostrix

• Manufacturer GlaxoSmithKline Biologicals,
  Rixensart, Belgium
• Application received July 3, 2004
• Proposed Indication Active booster immunization
  against diphtheria, tetanus and pertussis in
  individuals 10-18 years of age as a single im dose

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Tdap Boostrix, GSK

• Tetanus toxoid 5.0Lf
• Diphtheria toxoid 2.5Lf
• Pertussis toxoid 8µg
• Filamentous hemagglutinin 8µg
• Pertactin 2.5µg
• Al (as AlOH3) 0.3mg
• Preservative none
• Tetanus and diphtheria toxoids manufactured by
  ChironBehring GmbH Co., Marburg, Germany.

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Questions

• Are the available data adequate to support the
  efficacy of Boostrix in individuals 10-18 years
  of age?
• VOTE

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Questions contd

• Are the available data adequate to support the
  safety of Boostrix when administered to
  adolescents 10-18 years of age?
• VOTE

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Discussion

• Please identify any issues which should be
  addressed, including post-licensure studies.