The availability of an effective pneumococcal vaccine (Prevenar) makes it difficult to conduct clinical trials to assess the efficacy of pneumococcal conjugate vaccines with expanded serotype coverage, such as Prevenar 13® (Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)) using an unvaccinated control group.

Fortunately, the immune response induced by a new pneumococcal conjugate vaccine can be used to provide an assessment of its likely protective efficacy. Immunoglobulin G (IgG) binding antibodies, directed against the polysaccharide (sugar) found in the outer bacterial capsule, and the associated functionality of these antibodies (opsonophagocytic activity, OPA) provide immunological correlates of protection.

WHO technical report

The World Health Organization (WHO) issued a technical report series containing recommendations for the evaluation of new pneumococcal conjugate vaccines that reflect these principles. These WHO recommendations provided the basis for the clinical development of Prevenar 13. To maintain the link with the demonstrated efficacy of 7-valent pneumococcal conjugate vaccine (PCV7, Prevenar), it is critical that the immune responses induced by any new pneumococcal conjugate vaccine be compared in head-to-head comparative trials with the immune responses elicited by Prevenar.

Paediatrics

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Adults

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Paediatric Immunogenicity and Safety data

Immunogenicity and safety data were obtained from more than 4400 infants who received at least 1 dose of Prevenar 13 and from 354 older infants and young children. The safety and efficacy record of Prevenar was the basis for the clinical evaluation of Prevenar 13 and in most clinical trials, Prevenar 13 was compared with Prevenar.

In general, the phase 3 trials in infants were designed to demonstrate that, when given in different immunisation schedules (including the 2+1 schedule used in the UK), Prevenar 13:

• Elicits immune responses that are non-inferior to those induced by Prevenar for the 7 shared pneumococcal serotypes;
• Elicits acceptable immune responses to the 6 additional pneumococcal serotypes;
• Elicits an increase in antibody levels, as a result of a toddler dose of Prevenar 13, by comparing post-toddler dose levels with pre-toddler dose levels;
• Is compatible with other routine childhood vaccines;
• Has an acceptable safety profile;
• Can be manufactured using the intended commercial scale of production to yield vaccine preparations that consistently elicit the desired immune responses.

Comparative analysis of immune responses

The overall comparative analysis of immune responses to Prevenar 13 showed that Prevenar 13 elicits responses that are similar to Prevenar for the 7 pneumococcal serotypes common to both vaccines and that are within the set of pre-established criteria for non-inferiority. Prevenar 13 also stimulated an acceptable immunological response to the 6 additional serotypes, and is therefore likely to provide added protection, compared with Prevenar, against pneumococcal disease caused by these serotypes.
Data generated by the Phase III clinical trials programme also suggest that Prevenar 13 will be correspondingly effective when given in a national programme under a “2+1” schedule, as is the case in the UK.

Safety profile of Prevenar 13 similar to Prevenar

In clinical trials, Prevenar 13 was generally well tolerated and the level of reactogenicity observed was similar to that of other routinely used paediatric vaccines. The most common adverse events reported for Prevenar 13 were injection-site reactions, fever, irritability, decreased appetite, and increased and/or decreased sleep.425 Furthermore, the safety profile of Prevenar 13 was similar to that of Prevenar, of which more than 250 million doses have now been distributed worldwide and which has been adopted into the national immunisation programmes of more than 40 countries.
 

Adult Immunogenicity and Safety data

In adults 50 years and older, an antibody threshold of serotype-specific pneumococcal polysaccharide IgG binding antibody concentration associated with protection has not been defined.  For all pivotal clinical trials, a serotype-specific opsonophagocytosis assay (OPA) was used as a surrogate to assess potential efficacy against invasive pneumococcal disease.  OPA geometric mean titers (GMTs) measured 1-month after each vaccination were calculated. Immunogenicity response to Prevenar 13 was compared to the response to 23-valent polysaccharide vaccine (PPV).

Global regulatory application for the use of Prevenar 13 in adults was based on six pivotal Phase 3 studies involving more than 6,000 adults 50 years of age and older which demonstrated that:

• Prevenar 13 induced a non-inferior functional antibody response when compared to the currently licensed  PPV across all shared serotypes.
• Prevenar 13 induced a statistically significantly greater anti-pneumococcal functional antibody response compared to PPV across a majority of shared serotypes in vaccine-naïve and previously immunized adults 50 years of age and older.
• Prevenar 13 demonstrated a functional antibody response in individuals with certain co-morbidities such as chronic cardiovascular disease, diabetes mellitus, and chronic pulmonary disease.

Safety in adults

Safety was assessed in 6 clinical studies including 6,198 adults ranging in age from 50 to 95 years.

Prevenar 13 was found to have an acceptable safety profile and was generally well tolerated compared with PPV. Most commonly reported local and systemic adverse events:

• Redness, swelling, tenderness, hardness, and pain at the injection site, and limitation of arm movement
• Decreased appetite, headache, diarrhea, chills, fatigue, rash, and worsening of or new joint or muscle pain.

Previous vaccination history

It was found that Prevenar 13 can be safely administered to PPV-naïve adults ≥ 50 years as well as those adults previously immunised with PPV and thus may be given in absence of a reliable vaccination history.

Co-adminstration of other vaccines

Prevenar 13 can be coadministered with the seasonal trivalent inactivated influenza vaccine (TIV).

Concomitant use with other adult vaccines has not been investigated.

Summary of Product Characteristics can be found on electronic Medicines Compendium (eMC) click here to view.

Patient information Leaflet can be found on electronic Medicines Compendium (eMC) click here to view and download.