United States Concern for Europe with regards to Cervarix HPV vaccine

May 30, 2009

Authors: Cynthia Janak, Research Journalist, President of an International Coalition, Leslie Botha Researcher and Broadcast Journalist, Vice-President of an International Organization

This paper will focus on four areas: (1) European Public Assessment Report, (26/11/2008 Cervarix-H-C-721-II-04), (2) Cervarix© Product Information (PI_Cervarix.pdf.), (3) MHRA (Medicines and Healthcare products Regulatory Agency) March, 2009 and May, 2009.(4) Media reports. (brackets my emphasis)

Reports from around the world in regards to the HPV vaccines concern us greatly in the United States. Many of us have friends and family in Europe.We do not want to see any harm come to any citizen because of this kinship.That is why we felt it to be of paramount importance to add this information about the Cervarix © vaccine.

(1)European Public Assessment Report

1.1QUALITATIVE AND QUANTITATIVE COMPOSITION (page 2, title 2)

“absorbed on aluminium hydroxide, hydrated (Al(OH)3), L1 protein in the form of non-infectious virus-like particles (VLPs) produced by recombinant DNA technology using a Baculovirus expression system which uses Hi-5 Rix4446 cells derived from Trichoplusia ni.”

1. Contains 0.5 mg aluminum hydroxide

2.Trichoplusia ni (Hubner, 1800 – 1803) is nothing more than a
Cabbage Looper Moth.The DNA from this moth is being used in the construction of the L1 protein.There have been no studies conducted in regards to effects of insect DNA interaction with human DNA mentioned in this report.

1.2CLINICAL PARTICULARS (page 2 title 4) (4.1, second paragraph)“The indication is based on the demonstration of efficacy in women aged 15-25 years following vaccination with Cervarix and on the immunogenicity of the vaccine in girls and women aged 10-25 years.”

Page 5, Clinical studies, paragraph 1 – The efficacy of Cervarix was assessed in two controlled, double-blind, randomised Phase II and III clinical trials that included a total of 19,778 women aged 15 to 25 years.

Page 8, Bridging the efficacy of Cervarix from Young adult women to adolescents, paragraph 1 – In two clinical trials performed in girls and adolescents aged 10 to 14 years, all subjects seroconverted to both HPV types 16 and 18 after the third dose (at month 7) with GMTs at least 2-fold higher as compared to women aged 15 to 25 years. On the basis of these immunogenicity data, the efficacy of Cervarix is inferred from 10 to 14 years of age.

(It is not mentioned in this report which clinical trial the 10 – 14 age group participated in and the number of participants for this age group.The length of the study is also not known.Efficacy in this age group is only inferred.This age group receiving this vaccine is not relevant if there is no statistical benefit.)

4.2, Page 11, paragraph 1, – The need for a booster dose has not been established

Paragraph 2 – Girls aged less than 10 years: Cervarix is not recommended for use in girls below 10 years of age due to lack of data on safety and immunogenicity in this age-group.(The target age group to my knowledge is 9 – 26.)

4.4,Page 11 – Special warnings and precautions for use, paragraphs 4 and 5 – Vaccination is not a substitute for regular cervical screening or for precautions against exposure to HPV and sexually transmitted diseases.

As with any vaccine, a protective immune response may not be elicited in all vaccinees. Cervarix protects against disease caused by HPV types 16 and 18. Other oncogenic HPV types can also cause cervical cancer and therefore routine cervical screening remains critically important and should follow local recommendations. (If cervical screening still remains critically important then the vaccine is of no statistical benefit because it does not address the whole issue.)

Paragraph8 – Duration of protection has not fully been established. Timing and need of booster dose(s) has not been investigated.(Duration of protection is unknown therefore making this vaccine statistically irrelevant with further costs probable.)

4.5,Interaction with other medicinal products and other forms of interaction, page 12 – Use with other vaccines – Data have not been generated on the concomitant administration of Cervarix and other vaccines.

Use with hormonal contraceptive – In clinical efficacy studies, approximately 60% of women who received Cervarix used hormonal contraceptives. There is no evidence that the use of hormonal contraceptives has an impact on the efficacy of Cervarix.(Safety studies were not done in regards to the issue of hormonal contraceptives.This posses a real issue in regards to blood clot formation and this vaccine.)

4.8, Undesirable effects, page 12, paragraph 1, sentence 3 – In a pre-defined subset of subjects (Cervarix = 8,130 versus control = 5,786), adverse events were followed for 30 days after each injection.(No long term study into the adverse events was mentioned in this report.)

(2) Cervarix© Product Information

2.1 Page 14, paragraph 4 – As with any vaccine, a protective immune response may not be elicited in all vaccinees.(It is unknown what percentage of vaccinees are protected.)

Page 14, Effects on Fertility – Fertility was not affected in female rats given double the clinical dose of CERVARIX by intramuscular administration 30 days prior to mating.

Page 15 and 16, Genotoxicity – The genotoxic potential of CERVARIX has not been investigated. The adjuvant substance MPL has been tested for genotoxicity in a series of in vitro assays (bacterial mutation and chromosomal aberration) and an in vivo rat micronucleus test. Under the condition of these assays, MPL did not cause genetic damage.

Carcinogenicity.The carcinogenic potential of CERVARIX has   not been investigated.

The ability to perform tasks that require judgment, motor or cognitive skills – No studies on the effects on the ability to drive or use machines have been performed.

2.2(Adverse events not documented in a concise, detailed table format.Unable to determine percentage of participants affected with an adverse reaction to this vaccine.Potential population numbers as to this issue is not attainable making this vaccine a potential safety issue.)

(3) MHRA (Medicines and Healthcare products Regulatory Agency) – Summary of UK Safety Experience

3.1 – March 2009. Total number of reports received: 1,340.Total number of suspected reactions: 2,891 (reports received between April 14, 2008 and March 4, 2009.)[PDF. Attached]

1. Injection-site reactions: Total reactions – 418; Total reports – 312. These may occur at a frequency of more than 1 in 10 persons vaccinated.

2. Allergic reactions (including skin reactions not directly related to an injection-site reaction): Total reactions – 259; Total reports – 156.These may occur at a frequency between 1 in 10 persons (for non-serious types of allergic reactions such as rash and itching) to less than 1 in 10,000 persons vaccinated.

3. ‘Psychogenic’ events: Total reactions – 851; Total reports – 330.Such events can be associated with a wide range of temporary signs and symptoms including loss of consciousness, vision disturbance, injury, limb jerking

(often misinterpreted as seizure/convulsion), limb numbness or tingling, difficulty in breathing, hyperventilation, etc.

4. “Other recognized” reactions: Total reactions – 1125; Total reports – 626. This section includes other events recognized to be side-effects of Cervarix vaccine.

5. Suspected adverse reactions not currently recognized: Total reactions – 238; Total reports – 153. These suspected ADRs are not currently recognized as side effects of Cervarix vaccine.

3.2 – May 2009. Total number of reports received: 1,710, total number of suspected reactions: 3,774 (reports received between April 14, 2008 and May 21, 2009.)[PDF. Attached]

1. Injection- site reactions:
Total reactions – 591; Total reports – 430.

2. Allergic reactions:
Total reactions – 347; Total reports – 210.

3. ‘Psychogenic’ events:
Total reactions – 999; Total reports – 382.

4. “Other recognized” reactions:
Total reactions – 1418; Total reports – 765.

5. Suspected adverse reactions:
Total reactions – 419; Total reports – 243.

It is important that you refer to the documents attached to get a comprehensive overview of all the symptoms they consider to be ‘Psychogenic’, ‘Other recognized’ and Suspected events.All reactions stated in these reports are the same reactions that are being reported in the United States.

MHRA

Cervarix Human papillomavirus (HPV) vaccine (326Kb)
Human papillomavirus (HPV) vaccine (brand unspecified) (154Kb)

PG

Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.