Novartis announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Aflunov®, an investigational pre-pandemic avian influenza vaccine. The CHMP is endorsing the approval of Aflunov for active immunization against H5N1 subtype of Influenza A virus in adults 18 years of age and older. H5N1 (commonly referred to as avian or bird flu) accounts for most avian influenza outbreaks globally and is a serious health concern given its potential to evolve into a deadly pandemic strain at any time[6].
The CHMP recommendation serves as the basis for a European Commission licensing Decision. Based on the CHMP recommendation, a marketing authorization for Aflunov could be granted in all the European Union and EEA countries. The marketing authorization is expected to be granted before year-end.
"Upon approval, we expect Aflunov to be an important addition to our portfolio of pandemic preparedness solutions," said Andrin Oswald, Head of Novartis Vaccines and Diagnostics Division. "The onset of a pandemic can be very rapid, leaving little or no time to prepare. Vaccinating in advance may prevent the potential devastation of a pandemic outbreak."
H5N1 is presently the virus of greatest concern among all avian influenza viruses[7]. H5N1 is currently circulating in birds, poultry and many other animal species around the world and has already infected humans that have been in contact with infected animals[7],[8]. While human infections are continuing to rise, ability of the virus to spread from human to human has not been demonstrated yet[7]. To date, there have been more than 500 cases of serious illness and more than 300 deaths[5]. H5N1 morbidity and mortality rates remain significantly higher than those associated with seasonal influenza and any recent pandemic[4],[9],[10]. According to the World Health Organization (WHO), H5N1 has met all prerequisites for starting a pandemic except for the ability to spread efficiently and sustainably among humans[7].
Vaccines are considered the first line of defense against pandemic influenza[11]. Transmission of influenza virus during a pandemic can be rapid, leaving little or no time to prepare. Thus, proactive pre-pandemic vaccination to prime populations at risk or vaccine stockpiling may be a more adequate way to help protect those at risk of H5N1 infection[12], those who would form the first line of response during a potential pandemic, such as healthcare and emergency workers, and those critical to maintaining business and economic continuity.
In clinical trials, two doses of Aflunov demonstrated antibody titers considered protective in more than 85% of vaccinated individuals (homologous seroprotection rate)[13]. Aflunov was also shown to elicit cross-reactive antibodies against many of the H5 strains that have caused human disease[14]. Additionally, a single vaccination with Aflunov (H5N1, A/Vietnam/1194/2004) induced high and rapid serological response in subjects primed 6-8 years previously with two doses of a different surrogate H5 vaccine, having same formulation and including the same MF59 adjuvant as Aflunov but using the strain H5N3.
The EU regulatory filing for Aflunov will form the basis for further filings in other parts of the world including Asia, where H5N1 has been reported in many countries[7].
About Aflunov
Aflunov is an investigational influenza vaccine for the active immunization against H5N1 subtype of Influenza A virus. H5N1 is commonly referred as avian or bird flu. Aflunov contains the MF59 adjuvant and is intended for use before or upon declaration of a H5N1 avian influenza pandemic. In clinical trials Aflunov has demonstrated a broad and durable immune response[1],[2],[3], with tolerability comparable to seasonal adjuvanted vaccines[15]. It can be stockpiled for future use with sufficient shelf life.
About Novartis
Novartis Vaccines and Diagnostics is a division of Novartis, focused on the development of preventive treatments. The division has two businesses: Novartis Vaccines and Novartis Diagnostics. Novartis Vaccines is the world's fifth-largest vaccines manufacturer and second-largest supplier of flu vaccines in the US. The division's products also include meningococcal, pediatric and travel vaccines. Novartis Diagnostics, the blood testing business, is dedicated to preventing the spread of infectious diseases through the development of novel blood-screening tools that protect the world's blood supply.
Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2009, the Group's continuing operations achieved net sales of USD 44.3 billion, while approximately USD 7.5 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 102,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.
[1] Galli, G et al. (2009). Adjuvanted H5N1 vaccine induces early CD4 T cell response that predicts long-term persistence of protective antibody levels. Proceedings of the National Academy of Sciences; 106(10): 3877-3882. Available at: http://www.pnas.org/content/106/10/3877.full.pdf+html. Accessed on September 20, 2010.
[2] Stephenson I, et al. (2008). Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1. New England Journal of Medicine; 359:1631-1633. Available at: http://www.nejm.org/doi/pdf/10.1056/NEJMc0805274. Accessed on September 20, 2010.
[3] Novartis Data on File [V87P3].
[4] Centers for Disease Control and Prevention. (2008). Avian Influenza: Current Situation. Available at: http://www.cdc.gov/flu/avian/outbreaks/current.htm. Accessed on September 20, 2010.
[5] World Health Organization. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO. August 31, 2010. Available at: http://www.who.int/csr/disease/avian_influenza/country/
cases_table_2010_08_31/en/index.html. Accessed on September 20, 2010.
[6] Centers for Disease Control and Prevention. (2007). Key Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus. Available at: http://www.cdc.gov/flu/avian/gen-info/facts.htm. Accessed on September 20, 2010.
[7] World Health Organization. (2006). Avian influenza ("bird flu"). Available at: http://www.who.int/mediacentre/factsheets/avian_influenza/en/index.html. Accessed on September 20, 2010.
[8] Centers for Disease Control and Prevention. (2008). Questions and Answers About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus. Available at: http://www.cdc.gov/flu/avian/gen-info/qa.htm#4. Accessed on September 20, 2010.
[9] World Health Organization. (2009). Fact sheet no. 211. Influenza (Seasonal). Available at: http://www.who.int/mediacentre/factsheets/fs211/en. Accessed on September 20, 2010.
[10] Vaillant L, La Ruche G, Tarantola A, Barboza P, for the Epidemic Intelligence team at InVS. Epidemiology of fatal cases associated with pandemic H1N1 influenza 2009. Euro Surveill. 2009; 14(33): pii=19309. Available at: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19309. Accessed on September 20, 2010.
[11] World Health Organization. Responding to the avian influenza pandemic threat. Recommended strategic actions. Available at: http://www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_
GIP_05_8-EN.pdf. Accessed on September 20, 2010.
[12] Jennings LC, Monto AS, Chan PK, Szucs T, Nicholson KG(2008) Stockpiling influenza vaccines: A cornerstone of pandemic plans. The Lancet Infectious Diseases 8:650-658.
[13] Banzhoff, A. et al. (2009). MF59®-Adjuvanted H5N1 Vaccine Induces Immunologic Memory and Heterotypic Antibody Responses in Non-Elderly and Elderly Adults. PLoS ONE 4(2): e4384. Available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004384. Accessed on September 20, 2010.
[14] Banzhoff, A. et al. (2008). MF59-adjuvanted vaccines for seasonal and pandemic influenza prophylaxis. Influenza and Other Respiratory Viruses, 2:243-249.
[15] Novartis Data on File [V87P13].