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{\pard\sa900\fs50\f0\i Media Release\par}
Basel, 28 November 2006\line \line {\b Update on Tamiflu: 
no increase in drug resistance observed} \line Incidence of 
resistance rates remain low in treated patients (0.32% adults, 4.1% children)\line \line With 
the public interest in Tamiflu continuing, Roche keeps interested physicians and governments updated 
on current developments and today informs on the topic of resistance. There have been no new cases 
of resistance seen in patients infected with H5N1 virus (\u8216?bird flu\u8217?) since March 2005 and scientific 
data does not substantiate increased resistance to Tamiflu (oseltamivir). Roche is providing this update 
on the topic so that physicians and governments can be confident that Tamiflu can continue to be effectively 
used in the treatment and prophylaxis of seasonal and H5N1 influenza. \line \line "Over 
the last few months, there has been erroneous speculation that resistance to Tamiflu is increasing. 
This is an area that Roche and independent groups have been closely monitoring and there is no scientific 
evidence to suggest this is happening", said David Reddy, Roche\u8217?s Influenza Pandemic Taskforce 
Leader. 
\u8220?Governments can be confident that Tamiflu remains a critical drug, as recommended by the WHO, for stockpiling 
to prepare for an influenza pandemic and for physicians and patients to treat and prevent flu when it 
hits\u8221?.\line \line All H5N1 viruses that have been tested are susceptible to neuraminidase 
inhibitors like Tamiflu as described recently in the New England Journal of Medicine{\super {\pard\f0\li0\ri0\sa360\sl360\fs18 1\par}} .\line \line {\b Resistance 
not on the increase} \line As with any antiviral medication, there is a theoretical risk 
that a virus may emerge with decreased sensitivity to a drug. Roche monitors for any emerging resistance 
to Tamiflu both internally and externally via bodies such as the Neuraminidase Inhibitor Susceptibility 
Network, (NISN). The data, collected from thousands of patients worldwide who were treated with Tamiflu 
for seasonal influenza, generally indicate that the incidence of resistant viruses is rare (0.32% in 
adults and 4.1% in children).{\super {\pard\f0\li0\ri0\sa360\sl360\fs18 2\par}}  The higher 
incidence of resistant virus among children compared with 
adults appears to be related to higher levels of virus and longer duration of viral shedding. One small 
study in children in Japan did report a higher rate of resistance{\pard\f0\li0\ri0\sa360\sl360\fs18 {\super 3} \par}, 
however, in this study children 
received a different and often lower dosing schedule relative to the dosing used in children the West 
and some were dosed for less than the recommended 5 days. Surveillance during clinical use in Japan, 
where Tamiflu has been prescribed most often so far - 45 million patients have been treated with the 
antiviral - has shown that the low rates of resistance seen to date are not increasing. Of the few Tamiflu-resistant 
viruses so far identified, most cause less severe infections and are less capable of transmission. \line \line {\b Resistance 
to H5N1 avian virus} \line The possible development of anti-viral resistance is of concern 
for pandemic planning and preparedness. However, to date, there have only been three documented cases 
of Tamiflu resistance to avian influenza H5N1. {\super {\pard\f0\li0\ri0\sa360\sl360\fs18 4,5\par}}  
In one case, the prophylactic dose (75 mg daily) 
rather than the treatment dose (75 mg twice daily) was given to a patient already exhibiting clinical 
symptoms, thus under-dosing the patient and increasing the risk of resistance.{\super {\pard\f0\li0\ri0\sa360\sl360\fs18 4\par}}  
Once the twice daily 
treatment dose was provided, the patient recovered from their illness. Again this resistant virus was 
shown to cause less severe infection and was less capable of transmission. In the other two cases, the 
recommended dose and duration of oseltamivir was followed.{\super {\pard\f0\li0\ri0\sa360\sl360\fs18 5\par}}  
However, while one patient received treatment 
on the second day of illness, the other patient started treatment on the sixth day of illness. No further 
cases of resistance of H5N1 to Tamiflu have been identified or reported since March 2005, despite the 
number of infected patients increasing. A recent study has also shown that the responsiveness of H5N1 
viruses isolated in 2004 and 2005 to oseltamivir is about 10-fold higher than of H5N1 virus isolated 
in 1997 and of currently circulating seasonal (H1N1) viruses{\super {\pard\f0\li0\ri0\sa360\sl360\fs18 5\par}} . 
This suggests that the virus has become 
more responsive to Tamiflu over time. \line \line {\b About influenza} \line Influenza, 
commonly called the \u8216?flu\u8217?, is a serious disease and annual outbreaks and epidemics are caused by influenza 
A and B viruses. Influenza is a highly contagious viral illness and is characterised by a sudden onset 
of debilitating clinical symptoms which affect the entire body. Up to 500 million people are infected 
by influenza and up to 500,000 deaths are attributed to influenza each year. Influenza complications 
occur in all patient groups and include bronchitis, sinusitis, otitis media, and pneumonia. \line \line {\b About 
Tamiflu} \line Tamiflu is designed to be active against all clinically relevant influenza 
A and B viruses and works by blocking the action of the neuraminidase (NAI) enzyme on the surface of 
the virus. When neuraminidase is inhibited, the virus is not able to spread to and infect other cells 
in the body.\line It is licensed for the treatment and prophylaxis of influenza in children 
aged one year and above and in adults. \line \line {\b Roche\u8217?s efforts 
to support government pandemic stockpiling} \line The World Health Organization (WHO) 
advises that stockpiling antivirals in advance is presently the only way to ensure that sufficient supplies 
are available in the event of a pandemic. Roche has been working closely with WHO and national governments 
to ensure governments are aware of the importance of stockpiling antivirals in the event of a pandemic 
situation. Roche has received and fulfilled pandemic orders for Tamiflu from more than 75 countries 
worldwide. The magnitude of these orders varies with some countries, France, Finland, Iceland, Ireland, 
Luxembourg, Netherlands, New Zealand, Norway, Switzerland and UK stockpiling or intending to stockpile 
adequate Tamiflu to cover 20-40% of their population. Roche has also donated 5.125 million courses of 
Tamiflu treatment to the WHO for international rapid response and regional response to a pandemic influenza 
strain. \line \line {\b Roche and Gilead} \line 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\u8217? agreement, amended in November 2005, Gilead participates with Roche in the 
consideration of sub-licenses for the pandemic supply of oseltamivir. 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.\line \line {\b About 
Roche} \line Headquartered 
in Basel, Switzerland, Roche is one of the world\u8217?s leading research-focused healthcare groups in the 
fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the 
early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range 
of fronts to improving people\u8217?s health and quality of life. Roche is a world leader in diagnostics, 
the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 
2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division 
posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries and has 
R&D agreements and strategic alliances with numerous partners, including majority ownership interests 
in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (www.roche.com (http://www.roche.com)).\line \line {\pard\f0\li0\ri0\sa360\sl360\fs18 All 
trademarks used or mentioned in this release are legally protected.\par}\line \line {\b Additional 
information} \line - Roche 
Health Kiosk, Influenza (http://www.health-kiosk.ch/start_grip.htm)\line - 
About Tamiflu (http://www.roche.com/med_mbtamiflu05e.pdf)\line - About influenza (http://www.roche.com/med_mbackgrinfluenza05e.pdf)\line - 
WHO: Global influenza programme (http://www.who.int/csr/disease/influenza/en/)\line - WHO: Avian flu\line \line  (http://www.who.int/mediacentre/factsheets/avian_influenza/en/)\line {\pard\f0\li0\ri0\sa360\sl360\fs18 References\line 1. 
\u160?Webster, Robert G., Govorkova, Elena, A. \u8222?H5N1 Influenza \u8211? Continuing Evolution and Spread\u8220?, p.2174 
in: New England Journal of Medicine, N Engl J Med 355; 21, November 23rd, 2006\line 2. \u160?Roberts 
N. Treatment of influenza with neuraminidase inhibitors: virological implications. Philosophical Transactions 
of the Royal Society 2001;356(1416):1895-7.\line 3. \u160?Kiso M et al. Resistant influenza 
A viruses in children treated with oseltamivir descriptive study. Lancet 2004, 364:759-765\line 4. 
\u160?Le QM, Kiso M, Someya K, et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 2005;437:1108.\line 5. 
\u160?de Jong MD, Tran TT, Truong HK et al. Oseltamivir resistance during treatment of influenza A (H5N1) 
infection. N Engl J Med 2005;353:2667-2672.\line 6. \u160?Rameix-Welti MA et al. Natural variation 
can significantly alter the sensitivity of influenza A. Antimicrobial Agents and Chemotherapy 2006;50(11):3809-3815\line 7. 
\u160?Halloran ME et al. Antiviral effects on influenza viral transmission and pathogenicity: Observations 
from household-based trials. American Journal of Epidemiology online November 6 2006\par}
{\pard \par}
{\pard\sb180\f1\fs22 {\b F. Hoffmann-La Roche Ltd}\line 4070 Basel\line Switzerland \par}
{\pard\sb180\f1\fs22 Corporate Communications\line Roche Group Media Relations \par}
{\pard\sb180\f1\fs22 Tel. +41 61 688 88 88\line Fax +41 61 688 27 75\line www.roche.com \par}
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