GlaxoSmithKline (GSK plc) announced that the European Commission has granted a marketing authorisation for its H5N1 adjuvanted pre-pandemic vaccine, Prepandrix™, in all 27 EU member states. GSK is the first company to obtain a European licence for a pre-pandemic vaccine, thereby offering European governments the potential for protecting their population in advance or at the onset of an officially declared influenza pandemic.

"This vaccine marks a significant step in the world’s ability to cope with an influenza pandemic. It is testament to GSK scientists who have pioneered the approach to pre-pandemic vaccination, demonstrating our commitment to doing everything we can to help prevent the devastating effects of a pandemic and play our part in averting this potential public health crisis," said Jean-Pierre Garnier, CEO, GlaxoSmithKline.

According to the World Health Organisation (WHO), vaccines are the most important intervention for preventing influenza and reducing its health consequences during a pandemic.[1] There are two vaccine-based approaches that could be used in the event of a pandemic – a pandemic vaccine and a pre-pandemic vaccine.

Pandemic vaccines are produced as soon as a pandemic is declared, using the specific pandemic influenza strain. These vaccines will however, due to long manufacturing lead times, only be available four to six months after the onset of a pandemic, which will likely be too late for many of the victims of the first pandemic wave.[2]

A pre-pandemic vaccine is produced in advance of a pandemic. Such a vaccine is based on the currently circulating avian H5N1 influenza virus likely to cause a pandemic and has the ability to raise immune protection against potential drift H5N1 strains. Pre-pandemic vaccines therefore play a critical role in pandemic preparedness planning, with experts citing that immunisation with such stockpiled vaccines in advance or at the onset of a pandemic is the most effective strategy for protecting entire populations.[2,3]

"Pre-pandemic vaccination is an important strategy for addressing the current threat of a pandemic posed by H5N1," said Jean Stéphenne, President and General Manager GSK Biologicals. "GSK welcomes the EU approval for Prepandrix and remains committed to actively work with governments on their pandemic preparedness plans to help protect against the potentially devastating impact of a pandemic."

Novel adjuvant system
GSKs pre-pandemic H5N1 vaccine is formulated with a novel proprietary adjuvant system, which is designed to achieve a high immune response at a low dose of antigen which is long-lasting and active against a broad range of H5N1 strains.

H5N1 Influenza
H5N1 influenza (often referred to as avian influenza) infections can lead to severe disease in both birds and humans. To date, the WHO has reported 382 human cases of H5N1 infection from 14 countries resulting in 241 deaths.[4] Public health experts fear that this virus may evolve into a strain that is easily transmitted between people, triggering a worldwide pandemic.[5] Influenza pandemics are global outbreaks that involve viruses to which humans have little or no immunity. H5N1 is one such flu virus strain.

GSKs pre-pandemic H5N1 vaccine data
The EU license, with a current age indication from 18-60 years old, is based on data from a number of trials which evaluated the safety, reactogenicity, immunogenicity and cross-protection of the pre-pandemic vaccine using the Vietnam strain, which is a WHO recommended strain. In one of the pivotal trials, the vaccine, which utilises the antigen from the H5N1 A/Vietnam/1194/04 strain, demonstrated at least a four-fold increase in serum neutralising antibodies in 77% to 85% of subjects against three distinct H5N1 strain variants, A/Indonesia/5/05, A/Anhui/1/05 and A/turkey/Turkey/1/05 respectively.[6]

As it is not possible to predict the actual pandemic influenza virus strain, it is important for a pre-pandemic vaccine to show protection against a number of possible viral strains. The immune response elicited by GSKs pre-pandemic vaccine against H5N1 variants currently circulating in Asia, Europe and Africa demonstrates the possibility of protection against an eventual H5N1 pandemic strain. The vaccine has also shown cross-protection in preclinical studies, preventing mortality in 96% of cases following two doses of adjuvanted vaccine.[7] The studies also demonstrated that the vaccine is generally well tolerated.

GlaxoSmithKline supporting pandemic preparedness plans
GSK has previously announced its intention to donate 50 million doses of their pre-pandemic H5N1 vaccine to the WHO in support of its stockpile initiative. The donation would help establish a much needed stockpile of pre-pandemic vaccines that can be distributed to the world’s poorest countries at short notice by the WHO. Delivered over a three-year period, it would provide enough doses of vaccine for 25 million people at 2 injections per person. GSK supports this proactive strategy of worldwide stockpiling of H5N1 pre-pandemic vaccine which may be able to save millions of lives by protecting some of the most vulnerable populations in the world at the outbreak of a pandemic.

GSK has already signed contracts with the US and several European countries, such as Switzerland and Finland, and in 2007 sold £146 million of its pre-pandemic vaccine and bulk antigen.

AboutGlaxoSmithKline Biologicals
GSK Biologicals (GSK Bio), one of the world's leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline’s activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide. In 2007, GSK Bio distributed more than 1.1 billion doses of vaccines to 169 countries in both the developed and the developing world – an average of 3 million doses a day. Of those vaccine doses, more than one in every ten doses delivered were combination vaccines intended to prevent up to six diseases in one vaccine.

About GlaxoSmithKline
GSK continues to be committed to doing all it can to support governments and health authorities around the world in planning to respond to a global influenza pandemic prior to its outbreak and in the event one is officially declared. GSK has made substantial progress in its vaccine development programme and continues to investigate ways to further improve its pre-pandemic and pandemic vaccine strategies. To this end more than $2 billion has already been invested in developing a vaccine to combat H5N1 influenza, increasing the production capacity for influenza vaccines and GSK’s antiviral flu treatment Relenza®, in addition to ensuring the continuity of critical business operations and processes.

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 company information, visit GlaxoSmithKline at www.gsk.com.

Prepandrix and Relenza are trade marks of the GlaxoSmithKline group of companies.

References
[1] World Health Organization. Influenza Pandemic Preparedness and Response (report by the Secretariat). EB115/44. 20 January 2005
[2] Osterhaus Albert. Pre- or post-pandemic influenza vaccine? Editorial. Vaccine 2007; 25: 4983-4984.
[3] Gambotto A, Barratt-Boyes SM, de Jong MD, Neumann G, Kawaoka Y. Human infection with highly pathogenic H5N1 influenza virus. Lancet 2008; 371; 1464–75
[4] Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO: accessed 30 April, 2008
[5] Global pandemic influenza action plan to increase vaccine supply, WHO September 2006; accessed 7 Feb, 2008
[6] Leroux-Roels I, Bernhard R, Gérard P, Dramé M, Hanon E, et al. (2008) Broad Clade 2 Cross-Reactive Immunity Induced by an Adjuvanted Clade 1 rH5N1 Pandemic Influenza Vaccine. PLoS ONE 3(2): e1665. doi:10.1371/journal.pone.0001665
[7] Baras B, Stittelaar KJ, Simon JH, Thoolen RJMM, Mossman SP, et al (2008) PLoS ONE 3(1): e1401. doi:10.1371/journal.pone.0001401