Merck HPV Vaccine

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Merck HPV Vaccine

• Kathrin Jansen
• Eliav Barr
• Alan Shaw

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HPV Infection Causes Epithelial Neoplasia
Shedding of virus-laden cells
Cervical Surface
Viral assembly
Viral DNA in nucleus of infected basal cells
Normal Epithelium
Cervical Intraepithelial Neoplasia
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Mercks Investigational L1 VLP Vaccines

• Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP
  vaccine
• VLPs manufactured in S. cerevisiae
• Technology similar to that used for Mercks
  RECOMBIVAX HB Hepatitis B vaccine
• Yeast-derived vaccines administered to millions
  of children and adults
• Mercks Aluminum Adjuvant 225 mg per dose
• 0.5 mL injection volume
• 0, 2, 6 (month) dosing regimen

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Clinical Program Conducted in 3 Phases

• Phase I IIa
• Preliminary assessment of immunogenicity and
  tolerability of a broad range of doses of
  monovalent HPV L1 VLP vaccines
• Preliminary efficacy assessment of a monovalent
  HPV vaccine in women (proof of principle study)
• Phase IIb
• Immunogenicity and tolerability of a range of
  quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP
  vaccine dose formulations
• Logistics for large-scale international clinical
  trials
• Phase III
• Demonstrate that HPV L1 VLP vaccines reduce risk
  for
• acquisition of HPV infection and early endpoints
• development of a broad spectrum of HPV-related
  diseases

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Postdose 3 (Month 7) Anti-HPV RIA GMTs(mMU/mL)
with 95 CIs
1000
Geometric Mean Titer (mMU/mL)
Placebo
20/40/40/20 mg
100
40/40/40/40 mg
80/80/40/80 mg
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GMTs assoc. with Nat. Inf. 95 CI
HPV 11
HPV 16
HPV 18
HPV 6
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Protocol 005 Proof of Principle Efficacy Study

• Randomized, double-blind (in-house blinding),
  placebo-controlled study of HPV 16 vaccine pilot
  manufacturing material
• In 2392 young women with ?5 lifetime male sex
  partners
• Primary endpoint
• Persistent HPV 16 infection (PCR) and/or
• HPV 16-related CIN

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Proof of Principle Efficacy Study Primary
Efficacy Result

• Median Subject-Years at Risk (SYR) 1.41 years
  (17 months)
• Median duration of incident HPV infection 12.4
  months