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Gardasil 9

Gardasil® 9 suspension for injection.

Manufacturer
Merck Sharp & Dohme (UK) Limited
Label last updated
23 Sep 2024
Source
Official SmPC ↗

Nine-type HPV vaccine, offered at 12 to 13. It was never tested against a placebo - because HPV vaccination is already recommended in many countries - so it was compared with the older four-type vaccine instead.

56 findings, each with the section of the label it comes from.

Ingredients and materials

  • Nine HPV L1 proteins as virus-like particles per 0.5 ml dose: type 6 at 30 micrograms, type 11 at 40, type 16 at 60, type 18 at 40, and types 31, 33, 45, 52 and 58 at 20 micrograms eachs.2
  • The L1 proteins are produced in yeast cells (Saccharomyces cerevisiae CANADE 3C-5, strain 1895) by recombinant DNA technologys.2
  • Adsorbed on amorphous aluminium hydroxyphosphate sulfate adjuvant, 0.5 milligrams Als.2
  • The virus-like particles cannot infect cells, reproduce or cause diseases.5.1
  • Excipients: sodium chloride, histidine, polysorbate 80 (E433), borax (E285), water for injectionss.6.1
  • Declared essentially sodium-free, less than 1 mmol (23 mg) per doses.4.4

Manufacture, storage and handling

  • Shelf life 3 yearss.6.3
  • Store at 2C to 8C, do not freeze, keep the vial or syringe in the outer carton to protect from lights.6.4
  • Stable for 96 hours at 8C to 40C, or 72 hours at 0C to 2C, but these data are intended to guide professionals in case of a temporary temperature excursion only; use or discard at the end of the periods.6.4
  • May appear as a clear liquid with a white precipitate before agitation, and must be shaken well and inspected before use; discard if particulates are present or it appears discoloureds.6.6
  • Intramuscular injection, preferably the deltoid or the higher anterolateral area of the thighs.4.2, 6.6
  • Must not be injected intravascularly, subcutaneously or intradermally, and must not be mixed in the same syringe with any other vaccine or solutions.4.2
  • Two-dose schedule (0, 6 to 12 months) for 9 to 14 year olds, or a three-dose schedule (0, 2, 6 months); everyone 15 and over needs three dosess.4.2
  • If the second dose is given earlier than 5 months after the first, a third dose should always be administereds.4.2
  • Must not be mixed with other medicinal products; no compatibility studies exists.6.2

Safety findings

  • Contraindicated in hypersensitivity to the active substances or excipients, and in anyone who had a hypersensitivity reaction after a previous Gardasil 9 or Gardasil/Silgard doses.4.3
  • Vaccination should be postponed during acute severe febrile illness; a minor infection such as a mild upper respiratory tract infection or low-grade fever is not a contraindications.4.4
  • Vaccination may not result in protection in all recipients, and it will only protect against diseases caused by the HPV types targeted by the vaccine, so other precautions against sexually transmitted diseases should continues.4.4
  • The vaccine is for prophylactic use only and has no effect on active HPV infections or established clinical disease; it has not been shown to have a therapeutic effect and is not indicated for treating cancer, high-grade dysplastic lesions or genital warts, nor for preventing progression of other established HPV-related lesionss.4.4
  • It does not prevent lesions due to a vaccine HPV type in someone already infected with that type at the time of vaccinations.4.4
  • Vaccination is not a substitute for routine cervical screening, which 'remains critically important's.4.4
  • There are no data on use in individuals with impaired immune responsiveness, and those with impaired immune responsiveness from potent immunosuppressive therapy, a genetic defect, HIV infection or other causes may not respond to the vaccines.4.4
  • Give with caution in thrombocytopenia or any coagulation disorder because bleeding may occur after intramuscular injections.4.4
  • Long-term follow-up studies are still ongoing to determine the duration of protections.4.4
  • The need for a booster dose 'has not been established's.4.2
  • There are no safety, immunogenicity or efficacy data to support interchanging Gardasil 9 with bivalent or quadrivalent HPV vaccines, and studies using a mixed regimen were not performeds.4.2, 4.4
  • Fainting, sometimes with falling, can occur after or even before any vaccination, especially in adolescents, and can be accompanied by transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery; vaccinees should be observed for about 15 minutess.4.4
  • The decision to vaccinate should take into account the risk of previous HPV exposure and the potential benefits.4.4
  • Safety, immunogenicity and efficacy data are not available for children under 9 years of ages.4.2
  • Safety and immunogenicity in people who received immunoglobulin or blood-derived products in the 3 months before vaccination have not been studied in clinical trialss.4.5
  • Very common reactions: headache, and at the injection site pain, swelling and rednesss.4.8
  • Injection-site reactions were reported by 84.8 per cent of vaccinees within 5 days of any vaccination visit, and headache by 13.2 per cent within 15 days; most were mild or moderates.4.8
  • Listed as uncommon: lymphadenopathy, syncope sometimes accompanied by tonic-clonic movements, vomiting, urticaria, arthralgia, myalgia, asthenia, chills, malaise, injection site nodules.4.8
  • Listed as rare: hypersensitivity; anaphylactic reactions are listed at frequency not knowns.4.8
  • Post-marketing reports for the four-type vaccine, included because the two share four HPV types, list injection-site cellulitis, idiopathic thrombocytopenic purpura, anaphylactoid reactions, bronchospasm, acute disseminated encephalomyelitis and Guillain-Barre syndrome, all at frequency not knowns.4.8
  • Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or, for all events, establish a causal relationships.4.8
  • Pregnancy: post-marketing data indicate no malformative or foeto-neonatal toxicity, but the data are considered insufficient to recommend use during pregnancy, and vaccination should be postponed until the pregnancy is completes.4.6
  • A six-year pregnancy registry followed 180 women, of whom 69 pregnancies had known outcomes: miscarriage in 4.3 per cent and major birth defects in 4.5 per cent of live born infants, consistent with estimated background frequenciess.4.6
  • Breastfeeding: the vaccine can be used. In studies, immunogenicity and the adverse experience profile were comparable between breastfeeding and non-breastfeeding women, and there were no vaccine-related serious adverse experiences in breastfed infantss.4.6
  • Fertility: no human data on the effect on fertility are available; animal studies do not indicate harmful effectss.4.6
  • Overdose: no cases have been reporteds.4.9

Evidence and claims

  • 'Clinical studies evaluating the efficacy of Gardasil 9 against placebo were not acceptable because HPV vaccination is recommended and implemented in many countries', so the pivotal study used the four-type vaccine as the comparators.5.1
  • Efficacy against HPV types 6, 11, 16 and 18 was assessed using a bridging strategy showing comparable immunogenicity with the four-type vaccine, so efficacy against those types 'can be inferred to be comparable's.5.1
  • Efficacy against types 31, 33, 45, 52 and 58 was evaluated directly in the pivotal study against the four-type vaccine in women aged 16 to 26 (N=14,204: 7,099 on Gardasil 9, 7,105 on the comparator)s.5.1
  • Immunogenicity was assessed in women aged 27 to 45 and men aged 16 to 26, and bridged to girls and boys aged 9 to 15 rather than tested for disease outcomes in those groupss.5.1
  • Protection against disease is expressed as anticipated epidemiology percentages rather than trial results: approximately 90 per cent of cervical cancers, more than 95 per cent of adenocarcinoma in situ, 75 to 85 per cent of high-grade cervical lesions, 90 to 95 per cent of HPV-related anal cancer, and 90 per cent of genital wartss.5.1
  • The whole efficacy basis is: proven efficacy of the four-type vaccine, non-inferior immunogenicity between the two, direct efficacy against the five extra types in young women, and non-inferior immunogenicity in the other age groupss.5.1
  • The safety database is 15,776 individuals across 7 clinical trials, of whom 10,495 were aged 16 to 26 and 5,281 were adolescents aged 9 to 15; 0.1 per cent discontinued because of adverse experiencess.4.8
  • When the first dose was given with a combined diphtheria, tetanus, pertussis and polio booster, more injection-site reactions, headache and fever were reported, with differences under 10 per cent and mostly mild to moderates.4.8
  • In clinical studies, 60.2 per cent of women aged 16 to 26 used hormonal contraceptives during the vaccination period, and this did not appear to affect type-specific immune responsess.4.5
  • Preclinical: a repeat dose toxicity study in rats including single-dose toxicity and local tolerance revealed no special hazards to humans; in female rats there were no effects on mating performance, fertility or embryonic and foetal development, and antibodies against all 9 HPV types were transferred to offspring during gestation and lactations.5.3

Document and licensing

  • Marketing authorisation holder: Merck Sharp & Dohme (UK) Limited, Londons.7
  • First authorised 1 January 2021s.9
  • Text last revised 13 September 2024; the document carries a 2024 copyright notice for Merck & Co., Rahway, New Jerseys.10
  • The label states openly that a placebo-controlled efficacy trial was not considered acceptable, and that cancer protection figures are anticipated from epidemiology rather than measureds.5.1
  • Suspected reactions are reported through the MHRA Yellow Card schemes.4.8

Every line above is a summary of a statement in the manufacturer's own label, with the section number it comes from. Nothing has been added from any other source. The full list of flagged sentences is below, as it came out of the document.

Listed ingredients

Section 2 - qualitative and quantitative composition source ↗

1 dose (0.5 ml) contains approximately:
 Human Papillomavirus^1 Type 6 L1 protein^2,3 
 Human Papillomavirus^1 Type 11 L1 protein^2,3 
 Human Papillomavirus^1 Type 16 L1 protein^2,3 
 Human Papillomavirus^1 Type 18 L1 protein^2,3 
 Human Papillomavirus^1 Type 31 L1 protein^2,3 
 Human Papillomavirus^1 Type 33 L1 protein^2,3 
 Human Papillomavirus^1 Type 45 L1 protein^2,3 
 Human Papillomavirus^1 Type 52 L1 protein^2,3 
 Human Papillomavirus^1 Type 58 L1 protein^2,3 
 30 micrograms
 40 micrograms
 60 micrograms
 40 micrograms
 20 micrograms
 20 micrograms
 20 micrograms
 20 micrograms
 20 micrograms
 ^1Human Papillomavirus = HPV.
 ^2L1 protein in the form of virus-like particles produced in yeast cells (Saccharomyces cerevisiae CANADE 3C-5 (Strain 1895)) by recombinant DNA technology.
 ^3Adsorbed on amorphous aluminium hydroxyphosphate sulfate adjuvant (0.5 milligrams Al).
 For the full list of excipients, see section 6.1.

What these are, in plain English

  • yeast - Used in the laboratory to produce proteins. Traces can remain, which is why a yeast allergy can be a problem.
  • recombinant - Made by genetic engineering: the gene for one piece of the germ is put into a laboratory cell or bacterium, which then makes that piece.
  • aluminium - An aluminium salt. It is an adjuvant: it makes the immune system respond more strongly to the vaccine. Aluminium in vaccines has been used since the 1930s.
  • adjuvant - An added ingredient that makes the immune system react more strongly to the vaccine.

Other ingredients (excipients)

Section 6.1 source ↗

  • Sodium chlorideSalt. Used to keep the liquid at the same saltiness as the body.
  • HistidineAn amino acid, one of the building blocks of protein. Used to keep the liquid at a stable acidity.
  • Polysorbate 80 (E433)An emulsifier (E433), also used in some foods and cosmetics. It stops the ingredients separating.
  • Borax (E285)Also called sodium tetraborate (E285), a mineral salt used to hold the acidity steady.
  • Water for injectionsPurified water to the standard used for injected medicines. It is the liquid the other ingredients are dissolved in.
  • For adjuvant, see section 2.An added ingredient that makes the immune system react more strongly to the vaccine.
Audit trail: every flagged sentence in the document (65)

These are the sentences the mechanical filter pulled out, in the document's own words, grouped by section. They are what the briefing above was built from, kept here so you can check nothing was left out. Some are fragments and some are technical, which is why the briefing exists.

4.2 Posology and method of administration

  1. The need for a booster dose has not been established.

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • not been established - There is not yet enough evidence to state a conclusion.

    No data / not studied matched: not been established

  2. The safety and efficacy of Gardasil 9 in children below 9 years of age have not been established.

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • not been established - There is not yet enough evidence to state a conclusion.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpointsNo data / not studied matched: efficacy, have not been established

  3. No data are available (see section 5.1).

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • no data - The label is stating that no study has measured this. It is a statement about what was tested, not about what was found.

    No data / not studied matched: no data

4.3 Contraindications

  1. Individuals with hypersensitivity after previous administration of Gardasil 9 or Gardasil/Silgard should not receive Gardasil 9.

    Section 4.3 Contraindications source ↗

    In plain English

    • hypersensitivity - An allergic-type reaction, from a mild rash up to a severe reaction.

    Not recommended, contraindicated or restricted matched: should not receive

4.4 Special warnings and precautions for use

  1. The vaccine is therefore not indicated for treatment of cervical, vulvar, vaginal and anal cancer, high-grade cervical, vulvar, vaginal and anal dysplastic lesions or genital warts.

    Section 4.4 Special warnings and precautions for use source ↗

    Not recommended, contraindicated or restricted matched: not indicated

  2. There are no data on the use of Gardasil 9 in individuals with impaired immune responsiveness.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • no data - The label is stating that no study has measured this. It is a statement about what was tested, not about what was found.

    No data / not studied matched: no data

  3. There are no safety, immunogenicity or efficacy data to support interchangeability of Gardasil 9 with bivalent or quadrivalent HPV vaccines.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

4.5 Interaction with other medicinal products and other forms of interaction

  1. Safety and immunogenicity in individuals who have received immunoglobulin or blood-derived products during the 3 months prior to vaccination have not been studied in clinical trials.

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    In plain English

    • have not been studied - No trials have been run for this group or this situation.
    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.

    Animal, human or cell-line derived materialNo data / not studied matched: blood, have not been studied

4.6 Fertility, pregnancy and lactation

  1. Frequencies of miscarriage and major birth defects were 4.3 % of pregnancies (3/69) and 4.5 % of live born infants (3/67), respectively.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    Genetic engineering, vectors and GMOs matched: live

  2. However, these data are considered insufficient to recommend use of Gardasil 9 during pregnancy.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    In plain English

    • insufficient - Not enough to draw a conclusion from.

    Limited, insufficient or inconclusive matched: insufficient

  3. There were no vaccine-related serious adverse experiences reported in infants who were breast-feeding during the vaccination period.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    Rare or very rare serious events matched: serious adverse

4.8 Undesirable effects

  1. - Not known (cannot be estimated from the available data)

    Section 4.8 Undesirable effects source ↗

    In plain English

    • not known - The label's lowest band: the number of cases is too small, or the reporting too patchy, to work out how often it happens.

    No data / not studied matched: not known

  2. For events not observed in clinical trials the frequency is indicated as 'Not known'.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • not known - The label's lowest band: the number of cases is too small, or the reporting too patchy, to work out how often it happens.

    No data / not studied matched: not known

  3. Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • uncertain - The evidence does not settle the question.

    Limited, insufficient or inconclusive matched: not possible

5.1 Pharmacodynamic properties

  1. Gardasil 9 is an adjuvanted non-infectious recombinant 9-valent vaccine.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • recombinant - Made by genetic engineering: the gene for one piece of a germ is put into a lab cell or bacterium, which then makes that piece.

    Genetic engineering, vectors and GMOs matched: recombinant

  2. It uses the same amorphous aluminium hydroxyphosphate sulfate adjuvant as qHPV vaccine.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • adjuvant - An added ingredient that makes the immune system react more strongly to a vaccine.

    Adjuvants, carriers and immune-stimulating ingredients matched: adjuvant

  3. The efficacy of L1 VLP vaccines is thought to be mediated by the development of a humoral immune response.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  4. • demonstration of efficacy of qHPV vaccine to prevent persistent infection and disease related to HPV types 6, 11, 16 and 18 in females aged 16 to 45 years and males aged 16 to 26 years.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  5. • demonstration of non-inferior immunogenicity between Gardasil 9 and the qHPV vaccine for HPV types 6, 11, 16 and 18 in girls aged 9 to 15 years, women and men aged 16 to 26 years; efficacy for Gardasil 9 against persistent infection and disease related to HPV types 6, 11, 16, or 18 can be inferred to be comparable to that of the qHPV vaccine.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  6. • demonstration of efficacy against persistent infection and disease related to HPV types 31, 33, 45, 52 and 58 in girls and women aged 16 to 26 years, and

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  7. • demonstration of non-inferior immunogenicity against the Gardasil 9 HPV types in boys and girls aged 9 to 15 years, men aged 16 to 26 years and women aged 27 to 45 years, compared to girls and women aged 16 to 26 years.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.

    Efficacy, effectiveness and endpoints matched: non-inferior

  8. Efficacy and/or immunogenicity of Gardasil 9 were assessed in ten clinical studies.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  9. Clinical studies evaluating the efficacy of Gardasil 9 against placebo were not acceptable because HPV vaccination is recommended and implemented in many countries for protection against HPV infection and disease.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.
    • placebo - A dummy injection with no active ingredient, used as a comparison group in a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  10. Therefore, the pivotal clinical study (Protocol 001) evaluated the efficacy of Gardasil 9 using qHPV vaccine as a comparator.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  11. Efficacy against HPV types 6, 11, 16, and 18 was primarily assessed using a bridging strategy that demonstrated comparable immunogenicity (as measured by Geometric Mean Titres [GMT]) of Gardasil 9 compared with qHPV vaccine (Protocol 001, GDS01C/Protocol 009 and GDS07C/Protocol 020).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • geometric mean - An average used for antibody levels, because those vary over a huge range.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  12. In the pivotal study Protocol 001, the efficacy of Gardasil 9 against HPV types 31, 33, 45, 52, and 58 was evaluated compared to qHPV vaccine in women aged 16 to 26 years (N=14,204: 7,099 receiving Gardasil 9; 7,105 receiving qHPV vaccine).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  13. Studies supporting the efficacy of Gardasil 9 against HPV types 6, 11, 16, 18

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  14. Efficacy of qHPV vaccine against HPV types 6, 11, 16, 18

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  15. The efficacy and long-term effectiveness of qHPV vaccine against HPV 6-, 11-, 16-, and 18-related disease endpoints have been demonstrated in clinical studies in the PPE (Per Protocol Efficacy) population.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • effectiveness - How well it works in ordinary use in the real world.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: effectiveness

  16. In 16- through 26- year-old women (N=20,541) efficacy against HPV 16- and 18-related CIN2/3, AIS or cervical cancer was 98.2 % (95 % CI: 93.5, 99.8) based on follow-up to 4 years (median 3.6 years); efficacy against HPV 6, 11, 16 or 18-related diseases was 96.0 % (95 % CI: 92.3, 98.2) for CIN or AIS, 100 % (95 % CI: 67.2, 100) for VIN2/3, 100 % (95 % CI: 55.4, 100) for VaIN2/3, and 99.0 % (95 % [...]

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  17. In 24- through 45- year-old women (N=3,817) efficacy against HPV 6, 11, 16 and 18-related persistent infection, genital warts, vulvar and vaginal lesions, CIN of any grade, AIS, and cervical cancers was 88.7 % (95 %CI: 78.1, 94.8).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  18. In 16- through 26- year-old men (N=4,055) efficacy against HPV 6, 11, 16 or 18-related diseases was 74.9 % (95 % CI: 8.8, 95.4) for AIN 2/3 (median duration of follow-up of 2.15 years), 100.0 % (95 % CI: -52.1, 100) for penile/perineal/perianal intraepithelial neoplasia (PIN) 1/2/3, and 89.3 % (95 % CI: 65.3, 97.9) for genital warts (median duration of follow-up of 4 years).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  19. Immune responses, measured by GMT, for Gardasil 9 were non-inferior to immune responses for Gardasil (Table 3).

    Section 5.1 Pharmacodynamic properties source ↗

    Efficacy, effectiveness and endpoints matched: non-inferior

  20. Studies supporting the efficacy of Gardasil 9 against HPV types 31, 33, 45, 52, and 58

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  21. The efficacy of Gardasil 9 in women aged 16 to 26 years was assessed in an active comparator-controlled, double-blind, randomised clinical study (Protocol 001) that included a total of 14,204 women (Gardasil 9 = 7,099; qHPV vaccine = 7,105).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • randomised - A trial where people are assigned to groups by chance.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  22. Analysis of efficacy of Gardasil 9 against HPV types 31, 33, 45, 52, and 58 in the PPE^‡ population of 16 to 26 year old women

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  23. Additional efficacy evaluation of Gardasil 9 against vaccine HPV types

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  24. Since the efficacy of Gardasil 9 could not be evaluated against placebo, the following exploratory analyses were conducted.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.
    • placebo - A dummy injection with no active ingredient, used as a comparison group in a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  25. Efficacy evaluation of Gardasil 9 against cervical high grade diseases caused by vaccine HPV types in the PPE

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  26. The efficacy of Gardasil 9 against CIN 2 and worse related to vaccine HPV types compared to qHPV vaccine was 94.4 % (95 % CI 78.8, 99.0) with 2/5,952 versus 36/5,947 cases.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  27. The efficacy of Gardasil 9 against CIN 3 related to vaccine HPV types compared to qHPV vaccine was 100 % (95 % CI 46.3, 100.0) with 0/5,952 versus 8/5,947 cases.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  28. The efficacy of Gardasil 9 against cervical biopsy related to vaccine HPV types compared to qHPV vaccine was 95.9 % (95 % CI 92.7, 97.9) with 11/6,016 versus 262/6,018 cases.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  29. The efficacy of Gardasil 9 against cervical definitive therapy (including loop electrosurgical excision procedure [LEEP] or conisation) related to vaccine HPV types compared to qHPV vaccine was 90.7 % (95 % CI 76.3, 97.0) with 4/6,016 versus 43/6,018 cases.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  30. A subset of subjects is being followed up for 10 to 14 years after Gardasil 9 vaccination for safety, immunogenicity, and effectiveness against clinical diseases related to the HPV types in the vaccine.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • effectiveness - How well it works in ordinary use in the real world.

    Efficacy, effectiveness and endpoints matched: effectiveness

  31. In the long-term extensions of clinical studies Protocols 001 and 002, effectiveness was observed in the PPE population.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • effectiveness - How well it works in ordinary use in the real world.

    Efficacy, effectiveness and endpoints matched: effectiveness

  32. Incidence rates of vaccine HPV types related 6 month persistent infections in girls and boys observed during the study were 52.4 and 54.6 per 10,000 person-years, respectively, and within ranges of incidence rates expected in vaccinated cohorts of similar age (based on results from previous efficacy studies of Gardasil 9 and qHPV vaccine).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  33. The minimum anti-HPV titre that confers protective efficacy has not been determined.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.
    • titre - The measured level of antibodies in a blood sample.

    Efficacy, effectiveness and endpointsNo data / not studied matched: efficacy, not been determined

  34. Immune response to Gardasil 9 at Month 7

    Section 5.1 Pharmacodynamic properties source ↗

    Efficacy, effectiveness and endpoints matched: immune response

  35. Immunogenicity was measured by (1) the percentage of individuals who were seropositive for antibodies against the relevant vaccine HPV type, and (2) the Geometric Mean Titre (GMT).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • geometric mean - An average used for antibody levels, because those vary over a huge range.
    • titre - The measured level of antibodies in a blood sample.

    Efficacy, effectiveness and endpoints matched: geometric mean

  36. On the basis of this immunogenicity bridging, the efficacy of Gardasil 9 in girls and boys aged 9 to 15 years is inferred.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  37. These results support the efficacy of Gardasil 9 in the male population.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  38. In Protocol 004, anti-HPV antibody GMTs at Month 7 among women aged 27 to 45 years were non-inferior to anti-HPV antibody GMTs among girls and women aged 16 to 26 years for HPV 16, 18, 31, 33, 45, 52, and 58 with GMT ratios between 0.66 and 0.73.

    Section 5.1 Pharmacodynamic properties source ↗

    Efficacy, effectiveness and endpoints matched: non-inferior

  39. These results support the efficacy of Gardasil 9 in women aged 27 to 45 years.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  40. Persistence of immune response to Gardasil 9

    Section 5.1 Pharmacodynamic properties source ↗

    Efficacy, effectiveness and endpoints matched: immune response

  41. • for at least 5 years in women who were aged 16 to 26 years at time of vaccination with Gardasil 9, depending on HPV type, 78 to100 % of subjects were seropositive; however, efficacy was maintained in all subjects regardless of seropositivity status for any vaccine HPV type through the end of the study (up to 67 months postdose 3, median follow-up duration of 43 months postdose 3),

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  42. The clinical significance of this observation is not known.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • not known - The label's lowest band: the number of cases is too small, or the reporting too patchy, to work out how often it happens.

    No data / not studied matched: not known

  43. Seroconversion to all four antigens occurred in more than 96 % of the subjects.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • seroconversion - A rise in antibodies after vaccination, measured in the blood.

    Efficacy, effectiveness and endpoints matched: seroconversion

  44. The clinical relevance of the lower response is unknown.

    Section 5.1 Pharmacodynamic properties source ↗

    No data / not studied matched: is unknown

  45. The CD4 % or plasma HIV RNA was not affected by vaccination.

    Section 5.1 Pharmacodynamic properties source ↗

    Animal, human or cell-line derived material matched: plasma

  46. On the basis of this immunogenicity bridging, the efficacy of a 2-dose regimen of Gardasil 9 in girls and boys aged 9 to 14 years is inferred.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  47. The clinical relevance of these findings is unknown.

    Section 5.1 Pharmacodynamic properties source ↗

    No data / not studied matched: is unknown

  48. At Month 36, the GMTs in girls and boys aged 9 to 14 years receiving 2 doses at a 6-month interval (+/- 1-month) remained non-inferior to GMTs in women aged 16 to 26 years receiving 3 doses of Gardasil 9.

    Section 5.1 Pharmacodynamic properties source ↗

    Efficacy, effectiveness and endpoints matched: non-inferior

  49. Duration of protection of a 2-dose schedule of Gardasil 9 has not been established.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • not been established - There is not yet enough evidence to state a conclusion.

    No data / not studied matched: not been established

5.3 Preclinical safety data

  1. Gardasil 9 administered to female rats had no effects on mating performance, fertility, or embryonic/foetal development.

    Section 5.3 Preclinical safety data source ↗

    Animal, human or cell-line derived material matched: foetal

6.1 List of excipients

  1. For adjuvant, see section 2.

    Section 6.1 List of excipients source ↗

    In plain English

    • adjuvant - An added ingredient that makes the immune system react more strongly to a vaccine.

    Adjuvants, carriers and immune-stimulating ingredients matched: adjuvant

Read the whole document at the source ↗