Solna, 2009-05-12
Cervarix visar överlägset immunsvar i första jämförande studien
mellan de två tillgängliga vaccinerna mot livmoderhalscancer
GlaxoSmithKlines vaccin mot livmoderhalscancer, Cervarix, har visat signifikant kraftigare immunsvar
jämfört med Gardasil i den första storskaliga jämförande studien på de två godkända vaccinerna mot
1A
humant papillomvirus (HPV).
Enligt vad som meddelats denna vecka på den 25:e internationella
papillomviruskonferensen (IPV) i Malmö undersökte den jämförande studien två viktiga mått på
immunsvar: neutraliserande antikroppar och B-minnesceller, vilka man anser spelar en viktig roll för
hur bra ett vaccin skyddar kvinnor mot HPV-infektion och efterföljande livmoderhalscancer på lång
2A-7A
sikt.
I alla åldrar som studerats (kvinnor 18–45 år) var nivåerna av neutraliserande antikroppar med
Cervarix mer än två gånger högre än med Gardasil för HPV typ 16 och mer än sex gånger högre för
1B
HPV typ 18. Dessa resultat hade hög statistisk signifikans (p<0,0001).
Dessutom var andelen
kvinnor med påvisbara neutraliserande antikroppar i sekret från livmoderhalsen högre i gruppen som
1C
fick Cervarix.
Jämfört med Gardasil gav Cervarix också nästan tre (2,7) gånger fler B-minnesceller
1D
mot HPV 16 och 18.
Hillar Kangro, medicinsk rådgivare vid GlaxoSmithKline: ”Närvaron av neutraliserande antikroppar på
infektionsstället (livmoderhalsen) förefaller vara en viktig del av vaccininducerat skydd mot HPV. För
första gången har vi robusta kliniska bevis för att dessa två vacciner inte framkallar samma
immunsvar mot HPV typ 16 och 18, de två vanligaste cancerframkallande virustyperna. Vi är säkra på
att dessa resultat, tillsammans med nya resultat från fler viktiga studier som presenteras denna vecka,
visar potentialen hos Cervarix.”
Båda vaccinerna visade en kliniskt acceptabel säkerhetsprofil. Frekvensen av rapporterade symtom
8A
var högre med Cervarix. Reaktioner på injektionsstället var vanligast.
Följsamheten för att fullfölja
vaccinationsprogrammet var dock jämförbar för båda vaccinerna, vilket indikerar att båda tolererades
väl.
8B
De fullständiga resultaten från denna jämförande studie kommer att publiceras i en
vetenskapligt granskad tidskrift.
Resultaten från slutanalysen av fas III-studien (HPV-008) kommer också att presenteras på
konferensen och visar att Cervarix har stor och statistiskt signifikant effekt mot cellförändringar som är
förstadier till cancer och som är orsakade av de HPV-typer som ingår i vaccinet (HPV 16 och 18).
9A
Dessutom visar data att Cervarix ger typspecifikt skydd mot förändringar förknippade med andra
10A
cancerframkallande HPV-typer utöver HPV 16 och 18.
Därmed visades att den totala
skyddseffekten mot cellförändringar var större än vad som kan förväntas av ett vaccin som endast
11
skyddar mot HPV 16 och 18.
Frekvenserna av allvarliga biverkningar och medicinskt betydelsefulla tillstånd var likartade i studie9B
och kontrollgrupperna.
En tredje studie som kommer att presenteras i Malmö har visat att Cervarix ger höga och bestående
nivåer av antikroppar mot HPV 16 och 18 under 7,3 års uppföljning efter vaccination. Detta är den
12
längsta uppföljning som hittills rapporterats för något godkänt vaccin mot livmoderhalscancer.
Vacciner mot livmoderhalscancer ska ge långsiktigt skydd, eftersom kvinnor fortsätter att vara utsatta
för risk för HPV-infektion och cellförändringar i livmoderhalsen under hela livet.
Hillar Kangro, medicinsk rådgivare: ”Förebyggande av livmoderhalscancer är en folkhälsoprioritet i
såväl industriländer som i utvecklingsländer. Vi är mycket nöjda med dessa resultat och hur de
främjar förståelsen av den roll Cervarix har när det gäller att skydda kvinnor mot livmoderhalscancer.”
För mer information
Jonas Vikman, informationschef, 0705-638 220, [email protected]
Hillar Kangro, medicinsk rådgivare, 0761-147 204, [email protected]
Kommentarer till redaktörer
Om HPV 008
Effekt- och säkerhetsresultat från interimsanalysen av HPV-008-studien har tidigare publicerats i
Lancet.
13
De data som presenterats på den 25:e internationella papillomviruskonferensen (IPV) i
Malmö kommer från slutanalysen av studien. Ytterligare resultat blir tillgängliga när studieanalysen så
småningom är avslutad.
Om Cervarix
Vaccinationens huvudsakliga roll är att skydda kvinnor mot livmoderhalscancer. Eftersom kvinnor är i
riskzonen under den sexuellt aktiva perioden i livet krävs det av ett vaccin mot livmoderhalscancer att
det ger ett långsiktigt skydd och framkallar ett starkt immunsvar mot de vanligaste cancerframkallande
HPV-typerna.
Page 2
Cervarix utvecklades specifikt med ett nytt adjuvans, AS04, för att ge höga och bestående
15
antikroppsnivåer i syfte att ge långsiktigt skydd mot de vanligaste och aggressivaste HPV-typerna.
Det har visats att Cervarix i allmänhet tolereras väl. De vanligaste biverkningarna efter vaccination
16
omfattar smärta, rodnad och svullnad vid injektionsstället.
Hittills har Cervarix godkänts i 95 länder, däribland de 27 medlemsstaterna i Europeiska unionen (EU),
Australien, Brasilien, Sydkorea, Mexiko och Taiwan. Ansökningar om godkännande har inlämnats i
ytterligare mer än 20 länder, däribland Japan, Kanada och USA. GSK inlämnade också vaccinet till
Världshälsoorganisationen (WHO) för godkännande i september 2007.
Om HPV och livmoderhalscancer
17
Ungefär 100 typer av humant papillomvirus har hittills identifierats . Av dessa vet man att ungefär 15
18
virustyper orsakar livmoderhalscancer.
HPV typ 16 och 18 svarar globalt sett för ungefär 70 procent
av livmoderhalscancerfallen. Typ 45, 31 och 33 tillhör de näst vanligaste cancerframkallande HPV14B,19
typerna.
Persisterande infektion med cancerframkallande HPV-typer kan leda till onormala vaginalutstryk,
förstadier till cancer i livmoderhalsen och livmoderhalscancer. Globalt sett kommer mer än 500 000
kvinnor att nydiagnostiseras med livmoderhalscancer
20A
och 280 000 kvinnor kommer att dö av
20B
sjukdomen varje år.
GlaxoSmithKline Biologicals – GlaxoSmithKlines vaccinenhet, är ett av världens ledande
vaccinföretag och ledande inom innovation. Företaget är verksamt inom forskning, utveckling och
tillverkning av vacciner med över 30 vacciner godkända för försäljning och ytterligare 20 vacciner
under utveckling. GSK Biologicals har sitt huvudkontor i Belgien och 13 produktionsanläggningar
strategiskt placerade runt jordklotet. 2008 distribuerade GSK Biologicals 1,1 miljarder vaccindoser till
176 länder i både industri- och utvecklingsländer, vilket innebär i genomsnitt tre miljoner doser per
dag.
GlaxoSmithKline är ett av världens ledande forskningsbaserade läkemedels- och hälsoföretag och
engagerar sig för att förbättra människors livskvalitet genom att göra det möjligt för dem att vara mer
aktiva, må bättre och leva längre. Besök www.gsk.com för mer information.
®
Cervarix är ett registrerat varumärke som tillhör GlaxoSmithKline-koncernen.
®
Gardasil är ett registrerat varumärke som tillhör Merck & Co., Inc.
Page 3
Referenser
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
Einstein M et al. Comparative evaluation of immunogenicity of two prophylactic human papillomavirus
th
vaccines. Abstract presented at the 25 International Papillomavirus Conference (IPV) 8-14 May 2009;
Malmo, Sweden
Stanley M et al. Chapter 12: Prophylactic HPV vaccines: Underlying mechanisms. Vaccine. 2006; 24 Suppl
3:S106-13
Giannini SL et al. Enhanced humoral and memory B-cellular immunity using HPV16/18 L1 VLP vaccine
formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine 2006;
24:5937-5949
Inglis S et al. Chapter 11: HPV vaccines: Commercial Research & amp; Development. Vaccine 2006;24
Suppl 3:S99-S105
Villa LL. Vaccines against papillomavirus infections and disease. Rev Chilena Infectol. 2006; 23:157-163.
Banatvala J, Van Damme P, Oehen S. Lifelong protection against hepatitis B: the role of vaccine
immunogenicity in immune memory. Vaccine 2000;19(7-8):877-85.
Banatvala JE, Van Damme P. Hepatitis B vaccine - do we need boosters? J Viral Hepat 2003;10(1):1–6.
Einstein M et al. Immune response after primary vaccination course: a comparative trial of two HPV
th
prophylactic vaccines. Invited abstract presented at the 25 International Papillomavirus Conference (IPV) 814 May 2009; Malmo, Sweden
Paavonen J et al. Final phase III efficacy analysis of Cervarix™ in young women. Abstract presented at the
th
25 International Papillomavirus Conference (IPV) 8-14 May 2009; Malmo, Sweden
Skinner SR et al. Cross-protective efficacy of Cervarix™ against oncogenic HPV types beyond HPV-16/18.
th
Abstract presented at the 25 International Papillomavirus Conference (IPV) 8-14 May 2009; Malmo,
Sweden
Smith J S et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical
lesions: A meta-analysis update. Int J Cancer 2007; 121: 621-632
De Carvalho N et al. Immunogenicity and safety of HPV-16/18 AS04-adjuvanted vaccine up to 7.3y. Abstract
th
presented at the 25 International Papillomavirus Conference (IPV) 8-14 May 2009; Malmo, Sweden
Paavonen J et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against
infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III
double-blind, randomised controlled trial. Lancet 2007; 369: 2161–70
Bosch X et al. Epidemiology and Natural History of Human Papillomavirus Infections and Type-Specific
Implications in Cervical Neoplasia. Vaccine 2008; 26S: K1–K16
Aguilar JC. Vaccine adjuvants revisited. Vaccine 2007; 25: 3752-3762
Descamps D, Hardt K, Spiessens B et al. Safety of human papillomavirus (HPV)-16/18 AS04 adjuvanted
vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Human Vaccine, 2009; 55: 1-9.
WHO. Expert Committee on Biological Standardization. Guidelines to assure the quality, safety and efficacy
of recombinant Human Papillomavirus virus-like particle vaccines, accessed on 27/3/2009 at
http://screening.iarc.fr/doc/WHO_vaccine_guidelines_2006.pdf
Muñoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types
associated with cervical cancer. N Engl J Med 2003; 348: 518-527
Cohen J. High Hopes and Dilemmas for a Cervical Cancer Vaccine. Science 2005; 308: 618-621
World Health Organization. Initiative for Vaccine Research.
http://www.who.int/vaccine_research/diseases/hpv/en/ Accessed on February 13, 2009
Page 4
®
Cervarix IPV LOC Press Release Reference Pack
PAGE
1
CLAIM
GlaxoSmithKline’s cervical cancer
vaccine, Cervarix® has demonstrated a
significant higher immune response
compared to Gardasil® in the first largescale comparative study of the two
licensed HPV vaccines
SUPPORTING REFERENCE
LOCATION OF
CLAIM IN
REFERENCE
1A: Einstein M et al. Comparative evaluation of
immunogenicity of two prophylactic human
papillomavirus vaccines. Abstract presented at the
25th International Papillomavirus Conference (IPV) 814 May 2009; Malmo, Sweden
1A: Page 1;
paragraph 5
‘conclusions’; line 1
Higher immune response was observed with
Cervarix™ than Gardasil®
1
. . . the comparative study looked at two
key measures of immune response,
neutralising antibodies and memory B
cells, believed to play an important role in
how well a vaccine will protect women
from HPV infection and subsequent
cervical cancer over the long term.
2A: Stanley M et al. Chapter 12: Prophylactic HPV
vaccines: Underlying mechanisms. Vaccine. 2006;
24 Suppl 3:S106-13
Nonetheless, the overall data consistently show that
L1 VLPs induce high levels of serum neutralising
IgG, and the results of VLP vaccination both in
animal infections and clinical trials support the notion
that it is this activity that is critical for protection.
2A: Page S3/109;
column 1,
paragraph 1, lines
6-10
3A: Giannini SL et al. Enhanced humoral and
memory B-cellular immunity using HPV16/18 L1 VLP
vaccine formulated with the MPL/aluminium salt
combination (AS04) compared to aluminium salt
only. Vaccine.2006; 24:5937-5949
Based on studies in pre-clinical models, an effective
L1 VLP based prophylactic vaccine designed to
protect against HPV persistent infection and
subsequent cervical lesion development will need to
induce strong humoral immune responses. Preclinical models predict that induction of high levels of
neutralising antibody following vaccination with L1
VLPs will be important for an efficacious prophylactic
vaccine.
3A: Page 2;
column 1;
paragraph 3; lines
1-8
4A: Inglis S et al. Chapter 11: HPV vaccines:
Commercial Research &amp; Development.
Vaccine. 2006;24 Suppl 3:S99-S105
The successful animal studies suggested that, at a
minimum, a vigorous antibody response to the L1
protein of HPV would be required for a successful
vaccine and that sustained detectable levels of
antibody at the site of primary infection would be
necessary for continued protection.
4A: Page S3/101;
paragraph 2; lines
1-5
5A: Villa LL. Vaccines against papillomavirus
infections and disease. Rev Chilena Infectol. 2006;
23:157-163
Vaccines to prevent HPV infection aim to induce
neutralizing antibodies directed to conformational
epitopes of capsid proteins, which most probably will
be type specific. The protection against infection
depends on the amount of antibodies produced by
the host, its availability at the infection site and the
persistence of the neutralizing antibodies along time.
5A: Page 158;
column 2,
paragraph 2, lines
1-7
6A: Banatvala J, Van Damme P, Oehen S. Lifelong
protection against hepatitis B: the role of vaccine
immunogenicity in immune memory. Vaccine
2000;19(7-8):877-85.
Long-term protection against hepatitis B (HB)
disease is dependent on persistence of a strong
immune memory….The strength of immune memory
and of subsequent secondary immune response can
therefore be predicted by the antibody response
Page 5
6A: Page 877,
Abstract section
following primary vaccination.
7: Banatvala JE, Van Damme P. Hepatitis B vaccine
-- do we need boosters? J Viral Hepat 2003;10(1):1–
6
…protection is dependent on immune memory…
Page 6
7: Page 1,
Summary section
1
1
Across all ages studied (women 18 – 45),
neutralising antibody measures for
Cervarix® were more than two times
higher than those for Gardasil® forhuman
papillomavirus (HPV ) type 16, and more
than six times higher for HPV type 18.
These results were highly statistically
significant (p<0.0001).
1B: Einstein M et al. Comparative evaluation of
immunogenicity of two prophylactic human
papillomavirus vaccines. Abstract presented at the
25th International Papillomavirus Conference (IPV) 814 May 2009; Malmo, Sweden
In addition, the proportion of women with
detectable levels of neutralising antibodies
in cervical secretions was higher in the
group that received Cervarix®
1C: Einstein M et al. Comparative evaluation of
immunogenicity of two prophylactic human
papillomavirus vaccines. Abstract presented at the
25th International Papillomavirus Conference (IPV) 814 May 2009; Malmo, Sweden
1B: Page 1;
paragraph 4
‘results’; lines 1-3
In ATP cohort (seronegative/DNA-negative before
vaccination for HPV type analyzed), GMTs of serum
neutralizing antibodies were 2.3–4.8-fold higher for
HPV-16 and 6.8–9.1-fold higher for HPV-18 with
Cervarix™ than Gardasil®, across all age strata.
1C: Page 1;
paragraph 4
‘results’; lines 6-7
Positivity rates for neutralising antibodies (CVS)
were higher with Cervarix than Gardasil across all
age strata.
1
Compared to Gardasil®, Cervarix® also
produced nearly three (2.7) times more
memory B cells for HPV 16 and 18.
1D: Einstein M et al. Comparative evaluation of
immunogenicity of two prophylactic human
papillomavirus vaccines. Abstract presented at the
25th International Papillomavirus Conference (IPV) 814 May 2009; Malmo, Sweden
1D: Page 1;
paragraph 4
‘results’; lines 9-11
…frequency of circulating antigen-specific memory
B-cells in responders was 2.7 fold higher with
CervarixTM than Gardasil® for HPV-16 and HPV-18
2
Rates of solicited symptoms were higher
for Cervarix® with injection site reactions
being most common.
8A: Einstein M et al. Immune response after primary
vaccination course: a ccomparative trial of two HPV
prophylactic vaccines. Invited abstract presented at
the 25th International Papillomavirus Conference
(IPV) 8-14 May 2009; Malmo, Sweden
8A: Page 1;
paragraph 4
‘results’; lines 911
Both vaccines were generally well-tolerated.
Rates of solicited symptoms were higher for
Cervarix™, injection site reactions being
most common. Compliance was high (≥84%) for
both vaccines.
2
Compliance with the full vaccination
course was comparable for both vaccines
which indicates that both were well
tolerated.
8B: Einstein M et al. Immune response after primary
vaccination course: a ccomparative trial of two HPV
prophylactic vaccines. Invited abstract presented at
the 25th International Papillomavirus Conference
(IPV) 8-14 May 2009; Malmo, Sweden
8B: Page 1;
paragraph 4
‘results’; line 11
Compliance was high (≥84%) for both vaccines.
2
®
. .Cervarix provides a high and
statistically significant level of efficacy
against pre-cancerous lesions associated
with each of the HPV types included in the
vaccine (HPV 16 and HPV 18).
9A: Paavonen J et al. Final phase III efficacy
analysis of Cervarix™ in young women. Abstract
presented at the 25th International Papillomavirus
Conference (IPV) 8-14 May 2009; Malmo, Sweden
9A: Page 2;
paragraph 4
‘results’; lines 12
VE (96.1%CI) against HPV-16/18 CIN2+ in the ATPE was 92.9% (79.9;98.3) in the pre-defined primary
analysis
2
Cervarix® also provides type-specific
protection against pre-cancerous lesions
associated with some additional common
cancer-causing HPV types other than HPV
16 and HPV 18.
10A: Skinner SR et al. Cross-protective efficacy of
Cervarix™ against oncogenic HPV types beyond
HPV-16/18. Abstract presented at the 25th
International Papillomavirus Conference (IPV) 8-14
May 2009; Malmo, Sweden
Overall VE against CIN2+ associated with 14
oncogenic types, including vaccine types (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68) was
77.7% (63.5, 87.0; p <0.0001).
Page 7
10A: Page 1;
paragraph 3
‘results’; lines 79
2
2
Rates of serious adverse events and
medically significant conditions were
similar between study and control groups.
The efficacy demonstrated against any
lesion, regardless of HPV type in women
with or without prior infection, was greater
than would be expected for a vaccine
targeting only HPV types 16 and 18.
9B: Paavonen J et al. Final phase III efficacy
analysis of Cervarix™ in young women. Abstract
presented at the 25th International Papillomavirus
Conference (IPV) 8-14 May 2009; Malmo, Sweden
9B: Page 2;
paragraph 4
‘results’; lines 12
Rates of adverse events (including serious adverse
events and medically significant conditions) were
generally similar between groups.
11: Smith J S et al. Human papillomavirus type
distribution in invasive cervical cancer and highgrade cervical lesions: A meta-analysis update. Int J
Cancer 2007; 121: 621-632
11: Page 624;
column 2;
paragraph 4,
lines 1-3
In summary, this meta-analysis suggests that a
prophylactic vaccine against HPV 16/18 has the
potential to prevent more that two-thirds of
worldwide invasive cervical cancer (ICC) and half of
high-grade intraepithelial lesions (HSIL)
2
2
Results from a third study also presented
in Malmö show Cervarix® provides high
and sustained antibody levels against
HPV 16 and HPV 18 through the 7.3 years
of follow-up after vaccination. This is the
longest follow up reported to date for any
licensed cervical cancer vaccine.
12: De Carvalho N et al. Immunogenicity and safety
of HPV-16/18 AS04-adjuvanted vaccine up to 7.3y.
Abstract presented at the 25th International
Papillomavirus Conference (IPV) 8-14 May 2009;
Malmo, Sweden
Immune response and protection are
closely linked
2B: Stanley M et al. Chapter 12: Prophylactic HPV
vaccines: Underlying mechanisms. Vaccine. 2006;
24 Suppl 3:S106-13
12: Page 2;
paragraph 4
‘conclusions’;
lines 1-4
The HPV-16/18 AS04-adjuvanted vaccine offers
high and sustained antibody levels and 100%
seropositivity against both HPV-16 and HPV-18 up
to 7.3 years after vaccination with a favourable
safety profile. This is the longest follow-up reported
for any licensed HPV vaccine.
Nonetheless, the overall data consistently show that
L1 VLPs induce high levels of serum neutralising
IgG, and the results of VLP vaccination both in
animal infections and clinical trials support the notion
that it is this activity that is critical for protection.
2B: Page S3/109;
column 1,
paragraph 1, lines
6-10
3B: Giannini SL et al. Enhanced humoral and
memory B-cellular immunity using HPV16/18 L1 VLP
vaccine formulated with the MPL/aluminium salt
combination (AS04) compared to aluminium salt
only. Vaccine.2006; 24:5937-5949
Based on studies in pre-clinical models, an effective
L1 VLP based prophylactic vaccine designed to
protect against HPV persistent infection and
subsequent cervical lesion development will need to
induce strong humoral immune responses. Preclinical models predict that induction of high levels of
neutralising antibody following vaccination with L1
VLPs will be important for an efficacious prophylactic
vaccine.
3B: Page 2;
column 1;
paragraph 3; lines
1-8
4B: Inglis S et al. Chapter 11: HPV vaccines:
Commercial Research &amp; Development.
Vaccine. 2006;24 Suppl 3:S99-S105
The successful animal studies suggested that, at a
minimum, a vigorous antibody response to the L1
protein of HPV would be required for a successful
vaccine and that sustained detectable levels of
antibody at the site of primary infection would be
necessary for continued protection.
4B: Page S3/101;
paragraph 2; lines
1-5
5B: Villa LL. Vaccines against papillomavirus
infections and disease. Rev Chilena Infectol. 2006;
23:157-163
Vaccines to prevent HPV infection aim to induce
Page 8
5B: Page 158;
neutralizing antibodies directed to conformational
epitopes of capsid proteins, which most probably will
be type specific. The protection against infection
depends on the amount of antibodies produced by
the host, its availability at the infection site and the
persistence of the neutralizing antibodies along time.
column 2,
paragraph 2, lines
1-7
6B: Banatvala J, Van Damme P, Oehen S. Lifelong
protection against hepatitis B: the role of vaccine
immunogenicity in immune memory. Vaccine
2000;19(7-8):877-85.
Long-term protection against hepatitis B (HB)
disease is dependent on persistence of a strong
immune memory….The strength of immune memory
and of subsequent secondary immune response can
therefore be predicted by the antibody response
following primary vaccination.
6B: Page 877,
Abstract section
7B: Banatvala JE, Van Damme P. Hepatitis B
vaccine -- do we need boosters? J Viral Hepat
2003;10(1):1–6
7B:: Page 1,
Summarpy section
…protection is dependent on immune memory…
Page 9
2
2
Cervarix® provides protection against the
most common cancer-causing virus types
- HPV 16 and 18
[Cervarix] is the only vaccine to provide
additional, type-specific protection against
persistent infection caused by HPV 45 and
HPV 31
9B: Paavonen J et al. Final phase III efficacy
analysis of Cervarix™ in young women. Abstract
presented at the 25th International Papillomavirus
Conference (IPV) 8-14 May 2009; Malmo, Sweden
VE (96.1%CI) against HPV-16/18 CIN2+ in the ATPE was 92.9% (79.9;98.3) in the pre-defined primary
analysis
10B: Skinner SR et al. Cross-protective efficacy of
Cervarix™ against oncogenic HPV types beyond
HPV-16/18. Abstract presented at the 25th
International Papillomavirus Conference (IPV) 8-14
May 2009; Malmo, Sweden
9B: Page 2;
paragraph 4
‘results’; lines 12
10B: Page 1;
paragraph 3
‘results’; lines 12
VE (96.1% CI; p-value) against CIN2+ was: 100%
(82.2, 100; p<0.0001) for HPV-31/45 . . . Crossprotection was further substantiated by VE against
individual HPV types including 31&45.
3
The efficacy and safety results from the
interim analysis of the HPV 008 study
were previously published in the Lancet
13: Paavonen J et al. Efficacy of a prophylactic
adjuvanted bivalent L1 virus-like-particle vaccine
against infection with human papillomavirus types 16
and 18 in young women: an interim analysis of a
phase III double-blind, randomised controlled trial.
Lancet 2007; 369: 2161–70
13: See full
paper
See full paper
3
. . . HPV 45 and HPV 31, which, along
with type 33, are the most common cancer
causing HPV types after 16 and 18
worldwide
14A: Bosch X et al. Epidemiology and Natural
History of Human Papillomavirus Infections and
Type-Specific Implications in Cervical Neoplasia.
Vaccine 2008; 26S: K1–K16
14A: Page 8;
Figure 4
Figure 4. Type-specific HPV prevalence across the
spectrum of HPV related cervical diagnoses. Multiple
infections counted several times. ADC:
Adenocarcinoma; HSIL: High squamous
intraepithelial lesions; SCC: Squamous cervical
carcinoma
3
3
Cervarix® was specifically designed with a
novel adjuvant, AS04, to deliver high and
sustained levels of antibodies aimed at
providing long-term protection against the
most common and aggressive HPV types
15. Aguilar JC. Vaccine adjuvants revisited. Vaccine
2007; 25: 3752-3762
Cervarix® has been shown to be generally
well tolerated. The most common
symptoms after vaccination included pain,
redness and swelling at the injection site.
16: Descamps D, Hardt K, Spiessens B et al. Safety
of human papillomavirus (HPV)-16/18 AS04
adjuvanted vaccine for cervical cancer prevention: a
pooled analysis of 11 clinical trials. Human Vaccine,
2009; 55: 1-9.
“…This vaccine develops more rapid, intense and
long lasting immune response compared with control
vaccine in these high-risk groups, showing safety
and clinically acceptable local reactions similar to
other licensed hepatitis B vaccines. The AS04
adjuvant formulation has been tested as part of a
promising HPV vaccine development.”
“In conclusion, analysis of this large database shows
the HPV-16/18 ASO4-adjuvanted cervical cancer
Page 10
15: Page 3757;
paragraph 4;
lines 5-11
16: Page 1; column
1; paragraph 1;
Page 11
vaccine to have favourable safety profile in women
of all ages.”
lines 19-27
The incidence of solicited local symptoms (pain,
redness and swelling at the injection site) reported
during the 7-day period after each vaccine dose is
shown in Table 1.
Page 2; paragraph
4; lines 3-5
3
Approximately 100 types of human
papillomavirus have been identified to
date
17. WHO. Expert Committee on Biological
Standardization. Guidelines to assure the quality,
safety and efficacy of recombinant Human
Papillomavirus virus-like particle vaccines, accessed
on 27/3/2009 at
http://screening.iarc.fr/doc/WHO_vaccine_guidelines
_2006.pdf
17: Page 3;
paragraph 4;
lines 1-2
Over 100 different types of HPV have been identified
and molecularly characterized.
3
Approximately 100 types of human
papillomavirus have been identified to
date and, of these, approximately 15 virus
types are known to cause cervical cancer
18: Muñoz N et al. Epidemiologic classification of
human papillomavirus types associated with cervical
cancer. N Engl J Med 2003; 348: 518-527
18: Page 524;
column 2;
paragraph 4;
lines 1-5
‘Our epidemiologic classification, based on HPVtype–specific odds ratios and HPV prevalence
among patients and controls, identified 15 HPV
types as high-risk types (16, 18, 31, 33, 35, 39, 45,
51, 52, 56, 58, 59, 68, 73, and 82).’
4
HPV types 16 and 18 are responsible for
approximately 70 percent of cervical
cancers globally, with types 45, 31 and 33
among the next most common cancercausing HPV strains.12B,16
14B: Bosch X et al. Epidemiology and Natural
History of Human Papillomavirus Infections and
Type-Specific Implications in Cervical Neoplasia.
Vaccine 2008; 26S: K1–K16
14B: Page 8;
Figure 4
Figure 4. Type-specific HPV prevalence across the
spectrum of HPV related cervical diagnoses. Multiple
infections counted several times. ADC:
Adenocarcinoma; HSIL: High squamous
intraepithelial lesions; SCC: Squamous cervical
carcinoma
19: Cohen J. High Hopes and Dilemmas for a
Cervical Cancer Vaccine. Science 2005; 308: 618621
Bosch helped conduct an IARC coordinated
study published last year in the International Journal
of Cancer that examined the HPV types detected in
more than 3000 women from 25 countries who had
cervical cancer. The researchers found relatively
modest geographical differences, with two types,
HPV 16 and 18, occurring in more than 70% of the
cases.
Page 12
19: Page 619 ;
paragraph 3 ;
lines 1-9
4
Worldwide, more than 500,000 women will
be newly diagnosed and more than
280,000 women will die.
20A – 20B: World Health Organization. Initiative for
Vaccine Research.
http://www.who.int/vaccine_research/diseases/hpv/en/
20A: Page 1,
Disease burden,
Lines 3-4
Accessed on April 20, 2009.
Disease burden: Human Papillomavirus (HPV)
causes cervical cancer, and is the second biggest
cause of female cancer mortality worldwide with
288,000 deaths yearly. About 510,000 cases of
cervical cancer are reported each year with nearly
80% in developing countries: 68 000 in Africa, 77
000 in Latin America, and 245 000 in Asia.
Page 13
20B: Page 1,
Disease burden,
Lines 1-3
