Tamiflu Remains Fully Effective Against 94 Percent Of Circulating Influenza Viruses In Europe
Article Date: 20 Jan 2009 - 3:00 PST
Latest surveillance data coming through the European Centre for Disease Prevention and Control (ECDC) from virologists and clinicians indicates that the influenza A(H3N2) virus is the predominant strain in Europe so far this season.
Based on the data published by ECDC Roche confirms that the oral antiviral Tamiflu (oseltamivir) is fully active against influenza A(H3N2) and influenza B, which currently comprise 94 percent of circulating viruses in Europe this year.1
Tamiflu resistance reported in the 2008-2009 influenza seasons is confined to H1N1. No resistance has been seen with other circulating seasonal viruses - H3N2 and influenza B.
"Recent media reporting has elevated awareness of the H1N1 seasonal resistance seen this year in the United States and the Far East. However, in Europe the picture is different with H3N2 being the dominant strain so far. The circulating H3N2 viruses, which often cause a more severe illness than H1N1, are sensitive to oseltamivir, which means that oseltamivir will be active against the vast majority of influenza infections in Europe this season, if current trends continue," comments
Prof Albert Osterhaus, Head of Virology, Erasmus Medical Centre, Rotterdam. "It is important that doctors understand that oseltamivir remains an effective treatment for patients across Europe."
Vaccines are considered first line in the management of seasonal influenza, however, people who show symptoms or have been in close contact with an infected person may require more immediate intervention, such as Tamiflu, which can rapidly treat and prevent influenza.
European surveillance data
The ECDC reports that in the 2008-2009 season, influenza activity is increasing rapidly across Europe. The first countries to report high intensity of influenza activity were Portugal and Ireland. To date, medium or high intensity activity has been reported in nineteen countries.1 Of 2488 viruses which have been typed and sub-typed in Europe so far this influenza season, the majority, 2128, were H3N2, with a smaller proportion,141, subtype H1N1 and 219 were type B. The data to date indicate that influenza A (H3N2) and B viruses which Tamiflu is active against make up over 90 percent of the viruses circulating in Europe based on the latest information.1
US surveillance data
While influenza A(H1N1) has been the most common strain circulating in the US so far this season, the Centers for Disease Control and Prevention (CDC) has noted that it is early in the flu season and it is difficult to predict this season's dominant strain. Last season in the US, the dominant influenza strain changed from H1N1 to H3N2 in late January.
In December 2008, the CDC issued interim guidance for the 2008-2009 influenza season which recommends treatment with either zanamavir or Tamiflu in combination with rimantadine when influenza A(H1N1) virus infection or exposure is suspected.2 The CDC has reminded clinicians to remain alert for additional changes in recommendations as the influenza season progresses.
At the same time ECDC noted that the epidemiological situation was different in Europe and that therefore the same considerations might not apply in Europe. Infections with influenza A(H3N2), the predominant strain in Europe this season, or B viruses can be treated with either Tamiflu or zanamavir.
In addition to monitoring by government agencies, WHO collaborating laboratories and other public health institutions, Roche recently initiated the global Influenza Resistance Information Study (IRIS), which will include 1,200 patients per influenza season from 2008-2011. Roche also continues to support the activities of the Neuraminidase Inhibitor Susceptibility Network (NISN).
Sensitivity of H5N1 (bird flu) to Tamiflu
Recently published data confirms that the H5N1 avian influenza (bird flu) strain remains sensitive to Tamiflu. Greater than ninety nine percent of H5N1 samples studied did not exhibit mutations that confer oseltamivir resistance.3
According to Benjamin Schwartz, MD, CDC National Vaccine Program Office, "the mutations that have made the H1N1 virus resistant are unlikely to occur in a pandemic virus, so therefore we have not changed our recommendations for planning and stockpiling".4 Tamiflu remains the World Health Organization's "primary recommended antiviral agent of choice for the treatment of A(H5N1) virus infections".5
H1N1 Tamiflu resistant virus
The currently circulating Tamiflu resistant H1N1 virus was first identified in Norway in January 2008 and, subsequently, in other European countries where the use of Tamiflu is low, indicating that the resistance was likely to be naturally acquired and not due to Tamiflu use. This is further supported by data showing that patients with resistant virus had not taken Tamiflu or been in recent contact with anyone taking the drug.6 Clinical symptoms associated with the resistant H1N1 strain do not appear to be significantly worse than those with Tamiflu-sensitive virus.6
Difference between a pandemic strain of influenza and seasonal influenza
A pandemic strain of influenza is always of the A variety and is a completely new strain to which there will be no immunity whereas a seasonal strain of influenza is one that has previously been circulating, which may have changed slightly (antigenic drift) and to which a level of immunity exists.
Differences between seasonal strains
Human influenza viruses are usually classified into three broad types A, B and C according to differences in the antigenic properties of their external coat. Influenza A viruses are clinically the most important. Type C viruses do not cause significant human disease, so, only type A and B viruses are of concern. The A(H1) influenza virus is usually associated with mild epidemics, while the A(H3) virus is known to cause more severe illness. Currently circulating A virus subtypes are A(H3N2) and A(H1N1).
About Tamiflu
Tamiflu is designed to be active against all clinically relevant influenza viruses and works by blocking the action of the neuraminidase (NA) enzyme on the surface of the virus. When neuraminidase is inhibited, the spread of the virus to other cells in the body is inhibited. It is licensed for the treatment and prophylaxis of influenza in children aged one year and above and in adults. The most frequently reported adverse events in clinical studies were nausea, vomiting, and diarrhea. Tamiflu is available for the treatment of influenza in more than 80 countries worldwide. Tamiflu was approved based on studies in seasonal influenza. The magnitude of effect of Tamiflu in treating and preventing novel strains of influenza (such as those that may be involved in a pandemic or associated with avian flu) cannot be predicted. The WHO has recommended that higher doses and longer duration may be required
Roche and Gilead
Tamiflu was invented by Gilead Sciences and licensed to Roche in 1996. Roche and Gilead partnered on clinical development, with Roche leading efforts to produce, register and bring the product to the markets. Under the terms of the companies' agreement, amended in November 2005, Gilead participates with Roche in the consideration of sub-licenses for the pandemic supply of Tamiflu in resource-limited countries. To ensure broader access to Tamiflu for all patients in need, Gilead has agreed to waive its right to full royalty payments for product sold under these sub-licenses.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 80,000 people. Additional information is available on the Internet at
http://www.roche.com.
1. EISS - Weekly Electronic Bulletin Week 2 :05/01/2009-11/01/2009 16 January 2009, Issue N? 287
2. The Centres for Disease Control and Prevention (CDC). Interim Antiviral Guidance for 2008-09
http://www2a.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00279 Accessed 6 January 2009
3. Hill AW et al. Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza. Infections, Genetics and Evolution. 2008
4. 'Cost, resistance aired in HHS webcast on antivirals'. CIDRAP News. December 17 2008
http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/dec1708webinar.html Accessed 16 January 2009
5. Clinical management of human infection with avian influenza A(H5N1) virus. World Health Organization. 15 August 2007
http://www.who.int/csr/disease/avian_influenza/guidelines/ClinicalManagement07.pdf Accessed 16 January 2009
6. Hauge et al. Oseltamivir-Resistant Influenza Viruses A (H1N1), Norway, 2007-08. Emerg Infect Dis. 2009
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