Tuesday, March 4, 2008

International symposium reports on the use of antivirals [including TAMIFLU] in patients with H5N1

MISSISSAUGA, ON, March 4 /CNW/ - Physicians from countries affected by the deadly H5N1 influenza virus (bird or avian flu) have presented case reports about antiviral use in patients infected with H5N1, including treatment with the oral antiviral TAMIFLU(R) (oseltamivir). The physicians' reports were revealed this week at the International Symposium on Respiratory Viral Infections (ISRVI) in Singapore.(1)

TAMIFLU is approved for both the treatment and post-exposure prevention (prophylaxis) of influenza in adults and in children one year and older. Studies supporting the approval of TAMIFLU are based 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 as it has not been studied or approved in a pandemic scenario. The World Health Organization (WHO) has recommended that higher doses and longer treatment durations may be required to combat novel strains of influenza.

According to the WHO, the H5N1 virus has already killed 234 people in 12 countries.(2) In the most recent clinical management guidelines issued by the WHO, TAMIFLU remains the primary antiviral agent of choice for the treatment of H5N1 virus infections.(3)

Symposium findings

In Indonesia, of the total of 119 H5N1 human cases reported, 22 survived - an 18 per cent survival rate overall. Of the 119, 33 patients received no TAMIFLU, all of whom died. TAMIFLU was administered to the other 86 patients, with a 26 per cent survival rate overall. Time from onset of illness to initiation of treatment appeared to influence survival. Of the two patients who received TAMIFLU within 24 hours of illness onset, both survived. If given the drug within four days, 55 per cent survived (6/11), and 35 per cent survived if given TAMIFLU within six days (13/37).(4) The survival rate of those receiving it later than six days after illness onset was 18 per cent(9/49).(2)

Recent information about eight Vietnamese patients infected with H5N1 was also presented. All eight patients received TAMIFLU, however, all eight patients presented to the hospital later than five days after onset of illness. Only three of the eight patients survived reinforcing that treatment benefit is reduced for patients that receive the drug later in the course of illness.(4),(5) In two patients who were unable to take the drug orally due to the severity of their illness, physicians administered the drug by nasogastric tube and found it was well absorbed and there was a reduction in H5N1 virus in these patients.

Susceptibility of circulating H5N1 strains to TAMIFLU

These clinical findings are supported by animal data, also presented at ISRVI, which shows that oseltamivir treatment was effective against H5N1 influenza viruses representing different clades/subclades. However, higher doses were required for the more pathogenic H5N1 viruses.(6)

According to study author Dr. Elena Govorkova from St. Jude Children's Research Hospital, Memphis, US., multiple factors can affect the susceptibility of antiviral therapy with highly pathogenic H5N1 influenza viruses and it is reassuring that oseltamivir, in mouse models, demonstrates activity even to the most pathogenic circulating strains. She adds that antiviral drugs are an essential component for the early control of an influenza pandemic.

Data also confirms the low level of resistance reported to-date with TAMIFLU to H5N1 avian influenza in the field; there are only five cases of published reports of H5N1 resistance or reduced susceptibility to TAMIFLU to date.(7),(8),(9) Laboratory results have shown 96 per cent of H5N1 strains (53 out of 55) tested in the laboratory were sensitive to TAMIFLU.(10)

This compares to the around 14 per cent of isolates tested this year of the seasonal influenza A H1N1 virus showing resistance to TAMIFLU, reported at the conference.(11) It is important to note that these increased levels of resistance have only been reported spontaneously in this year's H1N1 (Solomon Islands) seasonal strain, and not an avian strain such as H5N1, and not in patients who have been administered TAMIFLU.(12)

Dr. David Reddy, Global Pandemic Task Force Leader at Roche noted that currently, they are seeing that TAMIFLU has been used as part of the clinical management of patients infected with H5N1 with only isolated cases of resistance being reported. This, he adds, is reassuring for governments that have stockpiled TAMIFLU for pandemic use while it is critical that the company and the medical community remain vigilant in order to nderstand this mutating virus and be best prepared for defence against a potential pandemic strain.

Roche has undertaken several research initiatives to study the use of TAMIFLU against the evolving H5N1 avian influenza virus, including collaborations with the National Institutes of Health (NIH), the Southeast Asia Influenza Clinical Trials Research Network, and other research institutions.

Flu 101 | Back to Basics

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. 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.

About pandemic influenza

An influenza pandemic occurs when a new strain of influenza A virus appears, against which the human population has no immunity resulting in several, simultaneous epidemics worldwide with enormous numbers of deaths and illness. The most severe influenza pandemics to date include: 'Spanish flu' A (H1N1): 1918 caused in excess of 30 million deaths worldwide; 'Asian flu' A (H2N2): 1958 caused one million deaths worldwide; 'Hong Kong flu' A (H3N2): 1968 caused 800,000 deaths worldwide in six weeks. The WHO believes that we are as close to the next pandemic as we have been at any time in the past 37 years, with two of the three widely-recognized prerequisites for a human pandemic met to date in the avian influenza outbreak in East Asia. Firstly, a new influenza virus strain has emerged (H5N1), and secondly, the virus has spread to humans. The final barrier will be the effective transmission of the virus from human to human.


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 royalty payments for product sold under these sub-licenses.

About Roche

Headquartered in Basel, Switzerland, Roche is a biotech company with a reputation for in-vitro diagnostics and drugs for cancer and transplantation, and with an ongoing interest in virology and therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system.

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