GlaxoSmithKline’s Synflorix is highly effective at preventing invasive pneumococcal disease

Results from the first randomised controlled European clinical trial of a pneumococcal conjugate vaccine (PCV) to examine impact on invasive pneumococcal disease (IPD) were published today in The Lancet and confirm that GlaxoSmithKline’s SynflorixTM is highly effective (93-100%[i]) at preventing IPD in infants younger than two years of age, who are most vulnerable to infectioni. With 47,369 children enrolled, this is the largest IPD effectiveness trial of PCVs in children.

The Finnish Invasive Pneumococcal Disease Vaccine Trial (FinIP) was conducted nationwide and tracked Synflorix effectiveness over a two-year period on average. The results show that Synflorix was highly effective when administered in either a three-dose (2+1) or a four-dose (3+1) schedule to infants starting at less than seven months of age (infants received two or three doses in their first year and a booster at two years of age)i.

For the first time in a clinical trial setting, effectiveness of a PCV utilised according to the infant 2+1 schedule, as used in many national immunisation programmes, was demonstrated (92%† against vaccine type IPD). Synflorix effectiveness against IPD caused by vaccine serotypes in a 3+1 schedule was 100%ǂ. Synflorix effectiveness against overall IPD, regardless of pneumococcal serotypes, was 93%*. In addition, high effectiveness** was observed in different catch-up schedules for older children. No safety concerns were noted during the studyi.

Dr William Hausdorff, Vice President and Vaccine Development Leader for Pneumococcal Vaccines, GSK Vaccines said: “IPD causes illness, hospitalisation and even death in Finnish children and across the world. These significant data show that Synflorix is an important public health tool in helping to reduce the burden of the disease.”

Vaccine-preventable IPD, such as meningitis, bacteraemic pneumonia and sepsis, causes death and illness in young children worldwide. Globally, IPD kills a child under five years of age every 40 seconds, with the majority of these living in the poorest countries, causing up to half a million deaths every year[ii].

The results from this randomised controlled clinical trial are also confirmed in post-implementation surveillance from four continents around the world[iii]-,[iv],[v],[vi],[vii],[viii],[ix],[x], which show consistent robust effectiveness against IPD, following vaccination with Synflorix.

On the basis of these encouraging results, GlaxoSmithKline plans to submit these data to regulatory authorities for inclusion in the Synflorix label.

† confidence interval: 58-100

ǂ confidence interval: 83-100

* confidence interval: 75-99

** 100%. confidence interval: 79-100

About the trial

Title: Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial.

Lead investigator: Dr Terhi Kilpi, National Institute for Health and Welfare, Tampere, Finland.

Background and aim: The FinIP trial was designed to assess vaccine effectiveness of 10-valent PHiD-CV (GlaxoSmithKline) against invasive pneumococcal disease (IPD).

Results: 13 culture-confirmed vaccine-type cases of invasive pneumococcal disease were detected in infants starting vaccination at less than seven months of age: none in the PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control groups. The estimates for vaccine effectiveness against vaccine type IPD were 100% (95% CI 83–100) for PHiD-CV10 3+1 and 92% (95% CI 58–100) for PHiD-CV10 2+1 groups. When considering all serotypes, there were a total of 16 cases of culture confirmed IPD: 14 in control groups and 2 in PHiD-CV10 groups (3+1 and 2+1 groups combined). The vaccine effectiveness estimate against all serotypes was 93% (95% CI 75-99).

About Synflorix

• Synflorix is a new generation paediatric pneumococcal conjugate vaccine (PCV) aimed at delivering protection against invasive pneumococcal diseases, such as meningitis, bacteraemic pneumonia and sepsis. Synflorix also helps to provide protection against pneumococcal middle ear infection, otherwise known as acute otitis media (AOM).
• Synflorix has been studied in 33 completed clinical trials to date.
• Since Synflorix was launched, nearly 100 million doses have been distributed worldwide.
• Licenses vary across the world. In Europe, Synflorix is indicated for active immunisation against invasive disease and acute otitis media caused by Streptococcus pneumoniae in infants and children from six weeks up to five years of age[xi].
• Synflorix has been made available to help protect children in over 90 countries, and has been designated as the vaccine of choice in more than 30 regional and national immunisation programmes around the world, including Finland, Netherlands, Sweden, New Zealand, Brazil, Ecuador, Peru, Kenya, Ethiopia and Pakistan.
• Synflorix was the first pneumococcal conjugate vaccine eligible under the Advance Market Commitment (AMC) to receive WHO ‘prequalification’.
• GSK will provide a minimum of 480 million doses of Synflorix to GAVI to help expand immunisation programmes against pneumococcal disease to 73 developing countries by 2023.

About pneumococcal disease

• Pneumococcal disease is a global health issue. Each year, Streptococcus pneumoniae (S. pneumoniae) infections are estimated to kill up to half a million children under five years of age, mostly in developing countriesii.
• Pneumococcal bacteria can cause life-threatening diseases such as meningitis, pneumonia and sepsis. S. pneumoniae can also cause less severe, but considerably more common diseases of the respiratory tract such as middle ear infections, sinusitis and bronchitisii.
• One child dies of pneumococcal disease every 40 seconds, and the majority of these live in the poorest countriesii.

References

[i] Palmu A et al. Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial. 2012. The Lancet.

[ii] World Health Organisation. Weekly epidemiological record 2012; 87:129-144.

[iii] DeWals P et al. Invasive pneumococcal disease in two birth cohorts vaccinated, respectively, with 2+1 PCV-7 or PHiD-CV-10 doses. ESPID 2011, The Hague, abstract 218.

[iv] Domingues et al. Effectiveness of one or more doses of 10-valent pneumococcal conjugate vaccine in Brazilian Children. 2012 ISPPD-8, Iguazu Falls, Brazil, 11-15th March, abstract # 764.

[v] Liphaus et al. Impact of 10-valent pneumococcal conjugate vaccine routine immunization schedule in incidence of pneumococcal meningitis in the state of Sao Paulo. 2012 ISPPD-8, Iguazu Falls, Brazil, 11-15th March, abstract # 736.

[vi] Scott et al. Impact of Introduction of 10-valent pneumococcal conjugate vaccine in Kenya on invasive pneumococcal disease among children under 5 years. 2012, ISPPD-8, Iguazu Falls, Brazil, 11-15th March, abstract # 211.

[vii] Kilifi health and demographic surveillance system PCVIS: the pneumococcal conjugate vaccine impact study. http://www.kemri-wellcome.org/pcvis-current%20disease%20surveillance. Accessed 13 November 2012.

[viii] Jokinen et al. 2012, Monitoring the effectiveness of the 10-valent pneumococcal conjugate vaccine (PCV10) in the the Finnish national vaccination programme (NVP). http://www.ktl.fi/attachments/suomi/osastot/roko/roto/isppd8_pneumokokkivaik_englanti_posteri.pdf. Accessed 13 November 2012.

[ix] Santos et al. Impact of the ten valent pneumococcal conjugated vaccine on pneumococcal infection of the population attending university hospital in Brazil. 2012 ICAAC, San Francisco, USA, 9-12th Sept.

[x] Afonso et al. Pneumococcal Vaccine Introduction in Brazil: A Preliminary Impact Analysis. 2012, ISPPD-8, Iguazu Falls, Brazil, 13-15th March.

[xi] GSK Biologicals. Synflorix™ EU Summary of Product Characteristics, 2011