Gsk Plc · LSE:GSK
Gsk — Conference Presentation (June 2007)
23 slides from Gsk's conference presentation, Jun 29, 2007
Slide 1: Study HPV-008: Phase III efficacy of GSK's Cervical Cancer Candidate Vaccine
Study HPV-008 Phase III study of the efficacy of GSK’s Cervical Cancer Candidate Vaccine in 15 to 25 year old women Planned Interim Analysis Results Paavonen, J. Et. Al. Lancet 2007 1
Slide 2: GSK's Cervical Cancer Vaccine Candidate: Composition
GSK’s Cervical Cancer Vaccine Candidate: Composition HPV-16 L1 VLP & HPV-18 L1 VLP Antigens Strong & Sustained Immune Response + AS04 Adjuvant System 2
Slide 3: HPV-008: Study Population
HPV-008: Study Population 35% 18,644 women vaccinated 16% 15 month interim analysis 3
Slide 4: HPV-008: Study Population
HPV-008: Study Population Unscreened women 15-25 years old Includes women with current or prior oncogenic HPV infection Efficacy evaluation in a broad population At entry : Oncogenic HPV infection Normal, low grade cytology and high grade cytology High Grade cytology was excluded from interim analys
Slide 5: HPV-008: Primary Efficacy Endpoint
HPV-008: Primary Efficacy Endpoint To assess efficacy of the vaccine in the prevention of histopathologically-confirmed CIN2+ associated with HPV-16 or -18 in the cervical lesion Assessed in women who are HPV DNA negative and seronegative at study entry for the corresponding HPV type considered in t
Slide 6: Results of the planned interim analysis: Efficacy against HPV-16/18 CIN2+
HPV-008: Results of the planned interim analysis Efficacy against HPV-16/18 CIN2+ 6
Slide 7: Interim Analysis: Complexity of the Data
HPV-008: Interim Analysis Complexity of the Data HPV-008 is unique in that it provides full characterization of HPV natural history and multiple infections in CIN lesions: High rate of prevalent HPV infections at study entry 23 CIN2+ cases with HPV 16/18 in the lesion triggered the interim analysis
Slide 8: Patterns of HPV Types in the CIN2+ Cases with HPV 16/18
Patterns of HPV Types in the 23 CIN2+ Cases with HPV 16/18 detected in the lesion Three HPV patterns were identified: 1. Single HPV type (HPV-16 or 18) in the CIN2+ lesion always preceded by infection with the same type in cytology samples 2. Multiple HPV types in the CIN2+ lesion with 16 or 18 infe
Slide 9: Multiple HPV types in CIN2+ lesion with no 16 or 18 infection in preceding samples
Multiple HPV types in the CIN2+ lesion with no 16 or 18 infection in preceding samples: 3 cases CERVICAL SAMPLES Month 12 Triggered Management Case Month 0 Month 6 Month 12 Punch Biopsy LEEP HPV CIN3: HPV-16/58 CIN3: HPV-58 1 113days after month 12 DNA 36days after month 12 Same lesion HPV 2 DNA HPV
Slide 10: Multiple HPV types in CIN2+ lesion with no 16 or 18 infection in preceding samples
Multiple HPV types in the CIN2+ lesion with no 16 or 18 infection in preceding samples: 3 cases CERVICAL SAMPLES Month 12 Triggered Management Case Month 0 Month 6 Month 12 Punch Biopsy LEEP CIN3: HPV-58 1 HPV HPV-58 HPV-58 HPV-58 CIN3: HPV-16/58 113d after mth 12 DNA 36d after mth 12 Same lesion HP
Slide 11: Multiple HPV types in CIN2+ lesion with no 16 or 18 infection in preceding samples
Multiple HPV types in the CIN2+ lesion with no 16 or 18 infection in preceding samples: 3 cases CERVICAL SAMPLES Month 12 Triggered Management Case Month 0 Month 6 Month 12 Punch Biopsy LEEP HPV CIN3: HPV-16/58 CIN3: HPV-58 1 HPV-58 HPV-58 HPV-58 113days after month 12 DNA 36days after month 12 Same
Slide 12: Multiple HPV types in CIN2+ lesion with no 16 or 18 infection in preceding samples
Multiple HPV types in the CIN2+ lesion with no 16 or 18 infection in preceding samples: 3 cases CERVICAL SAMPLES Month 12 Triggered Management Case Month 0 Month 6 Month 12 Punch Biopsy LEEP HPV CIN3: HPV-16/58 CIN3: HPV-58 1 HPV-58 HPV-58 HPV-58 113days after month 12 DNA 36days after month 12 Same
Slide 13: Multiple HPV types in CIN2+ lesion with no 16 or 18 infection in preceding samples
Multiple HPV types in the CIN2+ lesion with no 16 or 18 infection in preceding samples: 3 cases CERVICAL SAMPLES Month 12 Triggered Management Case Month 0 Month 6 Month 12 Punch Biopsy LEEP HPV CIN3: HPV-16/58 CIN3: HPV-58 1 HPV-58 HPV-58 HPV-58 113days after month 12 DNA 36days after month 12 Same
Slide 14: Multiple HPV types in CIN2+ lesion with no 16 or 18 infection in preceding samples
Multiple HPV types in the CIN2+ lesion with no 16 or 18 infection in preceding samples: 3 cases CERVICAL SAMPLES Month 12 Triggered Management Case Month 0 Month 6 Month 12 Punch Biopsy LEEP HPV CIN3: HPV-58 1 DNA HPV-58 HPV-58 HPV-58 CIN3: HPV-16/58 113days after month 12 36days after month 12 Same
Slide 15: Efficacy against HPV-16/18 CIN2+ (TVC-E)
Efficacy against HPV-16/18 CIN2+ (TVC-E) Additional- post hoc- analysis considering patterns of HPV types in preceding infection Vaccine Efficacy (97.9% CI) Endpoint Group N n % LL UL P-value HPV 7788 0 CIN2+ HPV-16/18 Control 7838 20 100 74.2 100 <0.0001 Pre-specified Case Definition based on PCR d
Slide 16: Multiple HPV types in CIN2+ lesion with no 16 or 18 infection in preceding samples
Multiple HPV types in the CIN2+ lesion with no 16 or 18 infection in preceding samples: 3 cases CERVICAL SAMPLES Month 12 Triggered Management Case Month 0 Month 6 Month 12 Punch Biopsy LEEP CIN3: HPV-58 Vaccine HPV HPV-58 HPV-58 HPV-58 CIN3: HPV-16/58 113days after month 12 DNA 36days after month 1
Slide 17: Results of the planned interim analysis: Efficacy beyond HPV 16/18 (persistent infection)
HPV-008: Results of the planned interim analysis Efficacy beyond HPV 16/18 (persistent infection) 17
Slide 18: Impact of Limited F/U time on Efficacy Against Persistent Infection
HPV-008: Impact of Limited F/U time on Efficacy Against Persistent Infection Interim analysis – 15 month mean follow-up Case counting for efficacy started after the first dose 6 month persistent infection Vaccine efficacy type 16/18 - 80.4% (70.4 - 87.4) ~ 70% of these infections were acquired befor
Slide 19: Efficacy Against HPV 31, 45 + 52: 6 Months Persistent Infection
HPV-008: Efficacy Against HPV 31, 45 + 52 6 Months Persistent Infection TVC-E (at least 1 dose) Type Vaccine (cases) Control (cases) Vaccine Efficacy 97.9% CI HPV-45 10 25 59.9% 2.6 – 85.2 HPV-31 47 74 36.1% 0.5 – 59.5 HPV-52 79 116 31.6% 3.5 – 51.9 In ∼70 % of these cases the onset of infection was
Slide 20: Efficacy Against Oncogenic HPV-types Beyond 16 & 18: 12 Months Persistent Infection
Efficacy Against Oncogenic HPV-types Beyond 16 & 18 12 Months Persistent Infection TVC-E (at least 1 dose) HPV-type endpoint Vaccine (cases) Control (cases) Vaccine Efficacy 97.9% CI Oncogenic HPV 100 137 27.1% 0.5 – 46.8 beyond 16 & 18 In ∼ 90 % of these cases the onset of infection was before comp
Slide 21: HPV-008: Safety Profile
GC) sk Aan Kline Biologicals HPV-008: Safety Profile
Slide 22: HPV-008: Overall safety profile
HPV-008: Overall safety profile Overall incidence of AEs reported during the 30-day period after each dose (diary card subset) Any symptom General symptoms Local symptoms Group N n % N n % N n % Overall HPV 3077 2913 94.7 3076 2614 85.0 3077 2807 91.2 number of women reporting a symptom Control 3080
Slide 23: HPV-008 Interim Analysis Conclusions
HPV-008 Interim Analysis Conclusions New science: First cervical cancer vaccine efficacy trial which provides full characterization of HPV natural history and multiple infections in CIN lesions 100% vaccine efficacy was observed against CIN2+ associated with HPV-16/18, following the analysis conside