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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/629473/2014

EMEA/H/C/000973

EPAR summary for the public

Synflorix

Pneumococcal polysaccharide conjugate vaccine (adsorbed)

This is a summary of the European public assessment report (EPAR) for Synflorix. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Synflorix.

What is Synflorix?

Synflorix is a vaccine. It is available as a suspension for injection that contains parts of the bacterium Streptococcus pneumoniae (S. pneumoniae).

What is Synflorix used for?

Synflorix is used to protect infants and children aged between six weeks and five years against invasive disease, pneumonia (infection of the lungs) and acute otitis media (infection of the middle ear) caused by S. pneumoniae. Invasive disease occurs when the bacterium spreads through the body causing serious infections such as septicaemia (blood infection), meningitis (infection of the membranes around the brain and spine) and pneumonia.

The medicine can only be obtained with a prescription.

How is Synflorix used?

The vaccination schedule for Synflorix depends on the age of the child and should be based on official recommendations.

• Infants aged between six weeks and six months are given three doses with an interval of at least one month between each dose, with the first dose usually given at two months of age. It is recommended that a fourth dose be given as a 'booster' at least six months after the third dose, preferably when the child is between 12 and 15 months of age. When Synflorix is given as part of a routine infant immunisation programme (when all infants in an area are vaccinated at around the

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same time), two doses may be given two months apart, from the age of two months, followed by a booster at least six months later.

•    Prematurely born babies (born between 27 and 36 weeks gestation) are given three doses with an interval of at least one month between each dose, with the first dose given at two months of age.

It is recommended that a fourth dose be given as a 'booster' at least six months after the third dose.

•    Infants aged between seven and 11 months are given two doses with an interval of at least one month between them. It is recommended that a third dose be given as a 'booster' at least two months after the second dose, during the child's second year of life.

•    Children aged between 12 months and five years are given two doses with an interval of at least two months between them.

The vaccine is given by injection into the thigh muscle in infants or into the shoulder muscle in young children. It is recommended that all children who receive the first dose of Synflorix complete the full vaccination course.

How does Synflorix work?

Vaccines work by 'teaching' the immune system (the body's natural defences) how to defend itself against a disease. When a person is given the vaccine, the immune system recognises the parts of the bacterium contained in the vaccine as 'foreign' and makes antibodies against them. The immune system will then be able to produce antibodies more quickly when it is exposed to the bacterium again. This helps to protect against the disease.

Synflorix contains small amounts of polysaccharides (a type of sugar) extracted from the 'capsule' that surrounds the S. pneumoniae bacterium. These polysaccharides have been purified, then 'conjugated' (attached) to a carrier to help them to be recognised by the immune system. The vaccine is also 'adsorbed' (fixed) onto an aluminium compound to stimulate a better response.

Synflorix contains the polysaccharides from 10 different types of S. pneumoniae (serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). In Europe, it is estimated that these are responsible for about 56 to 90% of the cases of invasive disease caused by S. pneumoniae in children under the age of five years.

How has Synflorix been studied?

Synflorix was evaluated in a large study involving over 30,000 infants aged below 7 months of age who were given either Synflorix or a comparator vaccine which was not active against S. pneumoniae. The children were followed up for an average of around two years to see how effective Synflorix was in preventing invasive disease.

Synflorix was also investigated in a large study involving around 24,000 children aged between 6 and 16 weeks that focussed mainly on the vaccine's benefit in preventing community acquired pneumonia. The children in this study were given either Synflorix or a comparator vaccine which was not active against S. pneumoniae and were followed up for an average of 30 months.

Another main study was carried out to determine whether Synflorix would prevent acute otitis media. The study involved almost 5,000 infants aged three months and compared an investigational vaccine that contains the same polysaccharides as Synflorix with another vaccine that is not active against S. pneumoniae infection (in this case, a vaccine against hepatitis A virus). The children were followed up until the end of their second year of life.

Synflorix

The ability of Synflorix to trigger the production of antibodies (immunogenicity) was assessed in one main study involving 1,650 healthy infants aged between six and 12 weeks. Synflorix was compared with another vaccine that is authorised in the European Union (EU) to protect children against S. pneumoniae infection, and which contains seven of the 10 polysaccharides included in Synflorix. The study compared the immunogenicity of the two vaccines against the different polysaccharides.

Additional studies looked at the effects of booster vaccinations and vaccinations in older infants and children. In particular, two clinical studies in children aged two to five years investigated the ability of Synflorix to produce antibodies in this age group compared with other age groups. The children received one dose of Synflorix in the first study and two doses in the second study.

What benefit has Synflorix shown during the studies?

In the invasive disease study, Synflorix was shown to be effective in protecting against invasive disease: no cases were seen among the 10,000 children given three doses of Synflorix and a booster, one case was among the 10,000 children given two doses of Synflorix and a booster and 12 cases were seen in 10,000 children given the comparator vaccine.

Synflorix was also shown to reduce the occurrence of pneumonia. In the large study that focused mainly on pneumonia, the percentage of children who had bacterial pneumonia was 2.3% (240 out of over 10,000) among those given Synflorix compared with 3% (304 out of over 10,000) among those given the comparator.

In the study looking at otitis media, the investigational vaccine containing the same polysaccharides as Synflorix was more effective than the comparator in preventing otitis media. The occurrence of the first episode of acute otitis media caused by S. pneumoniae was approximately halved among children who were given the vaccine compared with those given the comparator. Based on a comparison of the immune response of Synflorix with the vaccine used in the study, it is expected that Synflorix would provide similar protection against acute otitis media caused by S. pneumoniae.

In the immunogenicity study, Synflorix produced a similar response to the comparator vaccine for the majority of the S. pneumoniae polysaccharides they share in common. Synflorix was as effective as the comparator in triggering the production of antibodies against five of the polysaccharides that the two vaccines shared in common (4, 9V, 14, 18C and 19F), but it was less effective than the comparator for two (6B and 23F). For the three additional polysaccharides (1, 5, 7F), Synflorix was effective in triggering the production of antibodies.

The additional studies showed that Synflorix led to an increase in antibody production following booster vaccinations. The studies in infants and older children showed that although Synflorix produced a lower antibody response than the comparator vaccine, it fulfilled pre-defined criteria and was considered acceptable in this group. When Synflorix was tested in two to five years olds, the response to Synflorix was similar to the younger age group, with better results in children who received two doses.

What is the risk associated with Synflorix?

The most common side effects with Synflorix (seen in 1 in 10 people or more) are pain, redness and swelling at the injection site, fever, drowsiness, irritability and loss of appetite. The majority of these reactions were of mild to moderate severity and were not long lasting. For the full list of all side effects reported with Synflorix, see the package leaflet.

Synflorix must not be used in children who have a severe fever, but it can be given in children who have a mild infection such as a cold. For the full list of restrictions, see the package leaflet.

Why has Synflorix been approved?

The CHMP noted that the immune system's response to Synflorix was comparable to that of the comparator vaccine, which is also authorised for the protection of children against S. pneumoniae in the EU. The Committee also noted that Synflorix contains additional polysaccharides from the types of S. pneumoniae that are responsible for disease in Europe. The CHMP therefore decided that Synflorix's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Synflorix?

A risk management plan has been developed to ensure that Synflorix is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Synflorix, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Synflorix

The European Commission granted a marketing authorisation valid throughout the European Union for Synflorix on 30 March 2009.

The full EPAR for Synflorix can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Synflorix, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 10-2014.

Synflorix

EMA/629473/2014

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