GSK’s paediatric pneumococcal candidate vaccine Synflorix™ receives positive opinion in Europe

Serotypes included in the vaccine are responsible for up to 90% of invasive pneumoccal disease in young children in Europe. ^1,2,3

Issued: Thursday 22 January 2009, London UK

GlaxoSmithKline (GSK) announced today that the European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP)has issued a positive opinion and recommends approval of GSK’s paediatric pneumococcal candidate vaccine Synflorix™. The paediatric vaccine is proposed to be indicated for active immunisation against invasive pneumococcal disease (IPD) and middle ear infections (acute otitis media) caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years. The European Marketing Authorisation for the vaccine is expected to be granted in the coming months.

GSK’s pneumococcal candidate vaccineis expected to deliver broad public health benefit by offering coverage against three additional pneumococcal strains (serotypes 1, 5 and 7F) on top of the seven serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) which are covered in the existing paediatric pneumococcal vaccine.¹ Serotypes 1, 5 and 7F are responsible for a significant burden of disease, accounting for 5-25% of all IPD cases.⁴

“This novel 10-valent pneumococcal vaccine is designed to provide broad protection against major disease causing strains of pneumococcus with the potential of a significant public health benefit in Europe as well as globally,“ comments Jean Stéphenne, President and General Manager, GSK Biologicals. “Once approved, this important paediatric vaccine, which fits easily into existing vaccination schedules, will provide doctors with a new option in preventing life threatening pneumococcal disease and middle ear infections.”

Invasive disease

Invasive disease caused by Streptococcus pneumoniae (S. pneumoniae) bacteria include: meningitis, bacteraemic pneumonia, pleural empyema (pus / fluid build-up in the space around the lungs) and bacteraemia (blood infection). Nearly one in three cases of these potentially life-threatening diseases are currently not vaccine preventable in European children, as they are caused by strains not covered by the existing pneumococcal vaccine.⁵ Of these strains, serotypes 1 and 7F are on the rise in several Europe an countries and in many other parts of the world.^6,7,8,9 The 10 serotypes included in GSK’s candidate vaccine are responsible for up to 90% of IPD in young children, and are responsible for a significant proportion of IPD globally. ^{2,3,5,6,8,9,10}

Middle ear infections

In addition to broader coverage against invasive pneumococcal disease, GSK’s candidate vaccine is also designed to provide significant protection against the common middle ear infection, acute otitis media (AOM). It is estimated that three quarters of all children will experience at least one episode of AOM before they reach three years of age, with more than a third experiencing repeated infections.¹¹ The condition therefore places a high burden on children and their families¹², as well as a strain on healthcare resources.

Notes to editors

Synflorix™

GSK’s candidate vaccine is a 10-valent, pneumococcal conjugate vaccine. It was designed with polysaccharides derived from 10 different strains of pneumococcus. Eight are linked to a novel carrier protein ‘D’ derived from a second major paediatric pathogen – non-typeable Haemophilus influenzae (NTHi)¹³. This novel carrier protein is intended to minimise the possibility of immune interference when co-administered with other vaccines.¹⁴ GSK’s robust clinical development programme includes trials in Europe, as well as Africa, Asia and Latin America. Antibody responses to co-administered paediatric vaccines are similar to those observed when the vaccine is given alone, indicating that the candidate vaccine does not interfere with these co-administered paediatric vaccines.¹⁵

A prototype 11-valent pneumococcal vaccine formulation, which used the same novel approach in conjugation technology and contained the 10 serotypes covered by the current candidate vaccine (along with another serotype for which efficacy was not demonstrated), offered 33.6 % reduction of clinical acute otitis media in a European trial.¹⁶

The CHMP positive opinion is based on data from clinical trials in various countries across Europe (Czech Republic, Denmark, Finland, France, Germany, Norway, Slovakia, Sweden and Spain) as well as Latin America (Chile).

GSK submitted a file for this potentially life-saving candidate vaccine to the World Health Organization (WHO) for prequalification (PQ) in early 2008. PQ is a service provided by the WHO to facilitate access to medicines in less-affluent countries.

Pneumococcal disease

Pneumococcal bacteria can cause the life-threatening diseases meningitis, pneumonia and bacteraemia. These infections are called invasive pneumococcal disease and occur when the pneumococcal bacteria infect normally sterile areas of the body.  S. pneumoniae can also cause less severe, but considerably more common non-invasive diseases of the respiratory tract including, otitis media, sinusitis and bronchitis.¹⁷

Pneumococcal disease is a global health issue.  Each year, S. pneumoniae infectionsare estimated to kill one million children under five years of age worldwide.¹⁸  There are more than 90 distinct strains (serotypes) of pneumococcus but only 10-15 cause the vast majority of invasive disease in young children.¹⁹

Middle ear infections

Recurrent AOM often leads to surgical interventions. The insertion of tympanostomy tubes, or grommets, through the tympanum (ear drum) to allow aeration and drainage of the middle ear, is one of the most common paediatric surgical procedures in Europe. ^{20, 21} Otitis media is also one of the most frequent indications for the prescription of antibiotics in developed countries.²² Antibiotic resistance against the major causative pathogens, including S. pneumoniae, is increasing in many countries.^23,24,25 Vaccine prevention of S. pneumoniae otitis media may help to address the problem of antibiotic resistance.

GSK Biologicals is a global vaccine company which has shown itself to be a leader in innovation. The company is active in the fields of vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development. Headquartered in Belgium, GSK Biologicals has 14 manufacturing sites strategically positioned around the globe. In 2007 GSK Biologicals distributed 1.1 billion doses of vaccines to 169 countries in both developed and the developing world – an average of three million doses a day.

GSK Biologicals employs over 9,000 people worldwide including more than 1,600 passionate scientists engaged in research aimed at discovering innovative vaccines that contribute to the health and well-being of people of all generations around the world.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com

Enquiries:

UK Media enquiries:	Philip Thomson	(020) 8047 5502
	Alice Hunt	(020) 8047 5502
	David Outhwaite	(020) 8047 5502
	Stephen Rea	(020) 8047 5502
European Analyst/Investor enquiries:	David Mawdsley	(020) 8047 5564
	Sally Ferguson	(020) 8047 5543
	Gary Davies	(020) 8047 5503

Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2007.

References

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[2]   Zissis N, et al. Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive infections and acute otitis media in children. Eur J Pediatr (2004) 163: 364-368

[3]   GSP Summary Report for SAGE meeting, November 6-8, 2007.

[4]     Hausdorff WP, Bryant J, Paradiso PR et al. Which pneumococcal serogroups cause the most invasive disease: implications for conjugate vaccine formulation and use, part I. Clin Infect Dis 2000; 30:100-21

[5]    PneumoADip report. Last accessed Jan 2009

[6]    BrueggemannAB, Spratt BG. Geographic distribution and clonal diversity of Streptococcus pneumoniae serotype 1 isolates. J Clin Microbiol 2003; 41: 4966–70

[7]    IhekweazuCA, Dance DA, Pebody R et al. Trends in incidence of pneumococcal disease before introduction of conjugate vaccine: South West England, 1996-2005. Epidemiol Infect 2007;26:1-7.

[8]    Vergison A et al. Epidemiologic Features of Invasive Pneumococcal Disease in Belgian Children: Passive Surveillance IsNot Enough. Pediatrics 2006; 118: 801–9

[9]    Munoz-Almagro C et al. Emergence of Invasive Pneumococcal Disease Caused by Nonvaccine Serotypes in the Era of 7-Valent Conjugate Vaccine. Clin Infect Dis 2008; 46: 174–82.

[10]    Hausdorff WP, Feikin DR, Klugman KP. Epidemiologic differences among pneumococcal serotypes. Lancet  2005; 5:83-93

[11]   Klein JO. Otitis media. Clin Infect Dis 1994; 19: 823-32  

[12]    Stolk E, Mangen MJ, Wolleswinkel J et al.   Healthcare use and societal burden due to childhood otitis media in 7 EU Countries. Data presented at ESPID May 2008.

[13]  Pichichero ME. Evolving Shifts in Otitis Media Pathogens: Relevance to a Managed Care Organization. Am J Manag Care. 2005, 11:S192-S201

[14]    Forsgren A et al. Protein D of Haemophilus influenzae: A Protective Nontypeable H. influenzae Antigen and a Carrier for Pneumococcal Conjugate Vaccines. Clin Infect Dis 2008; 46: 726–31

[15]   Tejedor JC, Garcia-Sicilia J, Grunert D et al. Co-administration of the new 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with other routine paediatric vaccines. Data presented at ISPPD 2008

[16]   Prymula R, Peeters P, Chrobok V, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typeable Haemophilus influenzae: a randomized double-blind efficacy study. Lancet 2006; 367:740-4

[17]   WHO Pneumoccocal Conjugate Vaccine for childhood immunization position paper, March 2007.  Last accessed Dec 2008

[18]   World Health Organization. WHO fact sheet. Last accessed Dec 2008

[19]   Hausdorff WP, Bryant J, Paradiso PR, Siber GR. Which pneumococcal serogroups cause the most invasive disease: implications for conjugate vaccine formulation and use, part I. Clin Infect Dis 2000: 30:100-21

[20]   Haapkyla J, Karevold G, Kvaerner KJ, et al. Finnish adenoidectomy and tympanostomy rates in children; national variation. International Journal of Pediatric Otorhinolaryngoloy 2006; 70, 1569-1573

[21]   Karevold G, Haapkyla J, Pitka, et al Paediatric otitis media surgery in Norway. Acta Oto-Laryngologica, 2007; 127: 29-33

[22]   Cripps AW, OtczykaDC, Kydb JM. Bacterial otitis media: a vaccine preventable disease? Vaccine 2005; 23:2304-2310

[23]  Pichicero ME, Evolving shifts in otitis media pathogens: relevance to a managed care organization. Am J Manag Care 2005; 11:S192-S201

[24]   Leibovitz E. Acute otitis media in paediatric medicine. Current issue in epidemiology, diagnosis and management. Pediatr Drugs 2003; 5 (Suppl 1):1-12.

[25]   Cartwright K. Pneumococcal disease in Western Europe: burden of disease, antibiotic resistance and management. Eur J Pediatr  2002; 161:188-195.