Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Viral vaccines, Varicella zoster vaccines, ATC code J07BK01.

Mechanism of action
Varilrix produces an attenuated clinically inapparent varicella infection in susceptible subjects.
The presence of antibodies is accepted as evidence of protection, however, there is no established limit of protection for varicella disease.

Pharmacodynamic effects

Efficacy and effectiveness
The efficacy of GlaxoSmithKline (GSK)’s Oka varicella vaccines in preventing confirmed varicella disease (by Polymerase Chain Reaction (PCR) or exposure to varicella case) has been evaluated in a large randomised 

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multicountry clinical trial, which included GSK’s combined measles-mumps-rubella vaccine (Priorix) as active control. The trial has been conducted in Europe where no routine varicella vaccination was implemented at that time. Children aged 12-22 months received one dose of Varilrix or two doses of GSK’s combined measles- mumps-rubella-varicella vaccine (Priorix-Tetra) six weeks apart. Vaccine efficacy against confirmed varicella of any severity and against moderate or severe confirmed varicella was observed after a primary follow-up period of 2 years (median duration 3.2 years). Persistent efficacy was observed in the same study during the long-term follow-up periods of 6 years (median duration 6.4 years) and 10 years (median duration 9.8 years).
The data are presented in the Table below.

Group                   Timing           Efficacy against confirmed       Efficacy against moderate or severe varicella of any severity               confirmed varicella
GSK’s monovalent                Year 2                    65.4 %                                90.7% varicella (Oka) vaccine                              (97.5% CI: 57.2; 72.1)               (97.5% CI: 85.9; 93.9) (Varilrix)
Year 6(1)                  67.0%                                 90.3% 1 dose
(95% CI: 61.8; 71.4)                  (95% CI: 86.9; 92.8)
N = 2,487
Year 10(1)                  67.2%                                 89.5% (95% CI: 62.3; 71.5)                  (95% CI: 86.1; 92.1)
GSK’s combined              Year 2                      94.9%                                 99.5% measles, mumps,                                  (97.5% CI: 92.4; 96.6)                (97.5% CI: 97.5; 99.9) rubella and varicella
Year 6(1)                    95.0%                                 99.0% (Oka) vaccine
(95% CI: 93.6; 96.2)                  (95% CI: 97.7; 99.6)
(Priorix-Tetra)
2 doses              Year 10(1)                   95.4%                                 99.1%
N = 2,489                                     (95% CI: 94.0; 96.4)                  (95% CI: 97.9; 99.6) N = number of subjects enrolled and vaccinated
(1) descriptive analysis

In clinical trials, the majority of vaccinated subjects who were subsequently exposed to wild-type virus were either completely protected from clinical chickenpox or developed a milder form of the disease (i.e. low number of vesicles, absence of fever).

Effectiveness data, deriving from observation in different contexts (epidemic onset, case-control studies, observational studies, databases, models) suggest a higher level of protection and a decrease in the occurrence of cases of chickenpox following two doses of vaccine compared to a single dose.

The impact of one dose of Varilrix in reducing varicella hospitalisations and ambulatory visits among children were respectively 81% and 87% overall.

Post-Exposure Prophylaxis

Published data on the prevention of varicella following exposure to the varicella virus are limited.
In a randomised, double-blind, placebo-controlled study including 42 children aged between 12 months and 13 years, 22 children received one dose of Varilrix and 20 children received one dose of placebo within 3 days after exposure. Similar percentages (41% and 45%, respectively) of children contracted varicella, but the risk of developing a moderate to severe form of the disease was 8 times higher in the placebo group compared with the vaccinated group (relative risk = 8.0; 95% CI: 1.2; 51.5; P=0.003).

In a controlled study including 33 children aged between 12 months and 12 years, 15 received varicella vaccine (13 subjects received Varilrix and 2 subjects received another Oka strain varicella vaccine) up to 5 days after exposure and 18 subjects were not vaccinated. When considering the 12 children vaccinated within 3 days after exposure, vaccine effectiveness was 44% (95% CI: -1; 69) in preventing any disease and 77% (95% CI: 14; 94) in preventing moderate or severe disease.
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In a prospective cohort study (with historic attack rates as control), 67 children, adolescents or adults received varicella vaccine (55 subjects received Varilrix and 12 subjects received another Oka strain varicella vaccine) within 5 days after exposure. Vaccine effectiveness was 62.3% (95% CI: 47.8; 74.9) in preventing any type of disease and 79.4% (95% CI: 66.4; 88.9) in preventing moderate and severe disease.

Individuals at high risk of severe varicella

Patients suffering from leukaemia, patients under immunosuppressive treatment (including corticosteroid therapy) for malignant solid tumour, for serious chronic diseases (such as chronic renal failure, auto-immune diseases, collagen diseases, severe bronchial asthma) or following organ transplantation, are predisposed to severe natural varicella. Vaccination with the Oka-strain has been shown to reduce the complications of varicella in these patients.

Immune response after subcutaneous administration

Healthy individuals
In children aged 11 months to 21 months the seroresponse rate, when measured by ELISA 6 weeks after vaccination, was 89.6% after one vaccine dose and 100% after the second vaccine dose.

In children aged 9 months to 12 years the overall seroconversion rate, when measured by Immunofluorescence Assay (IFA) 6 weeks after vaccination, was >98% after one vaccine dose.

In children aged 9 months to 6 years the seroconversion rate, when measured by IFA 6 weeks after vaccination, was 100% after a second vaccine dose. A marked increase of antibody titres was observed following the administration of a second dose (5 to 26-fold increase of geometric mean titres).

In subjects aged 13 years and above the seroconversion rate, when measured by IFA 6 weeks after vaccination, was 100% after the second vaccine dose. One year after vaccination, all subjects tested were still seropositive.

Individuals at high risk of severe varicella

Limited data from clinical trials have shown immunogenicity in subjects at high risk of severe varicella.

Pharmacokinetic Properties

5.2        Pharmacokinetic properties

Evaluation of pharmacokinetic properties is not required for vaccines.