Roche announces that it has in less than two months completed the systematic evaluation of around 200 third parties interested in helping with the manufacture of Tamiflu® (oseltamivir) 12 potential partners have been identified whose addition to Roche’s Global Tamiflu Supply Network would enhance available supply. As a next step, these potential partners will be invited for further in depth negotiations.

William M. Burns, CEO Roche Pharma Division, commented: “Following our open invitation to third parties we have established a short list of partners who can be ready to expand the capacity beyond 300 million treatments annually by 2007. As yet we have not identified anyone who could significantly speed up the agreed delivery timelines for the first half of 2006, but we have been able to identify partners to ensure against breakdowns in supply, and partners to broaden geographic coverage. Based on the current orders we have received from governments around the world, our capacity to produce 300 million treatments by 2007 is significantly ahead of demand.”

Sub-licences for China and other countries
Roche and Shanghai Pharmaceutical Group have signed the first sub-licensing agreement for the overall production of Tamiflu for pandemic use in China . Roche is also in negotiations for local partnerships in other countries.

Expansion of the Global Tamiflu Supply Network
After systematic screening, Roche production experts started detailed negotiations with twelve companies who met the defined criteria in terms of quality, technical ability, capacity and the speed of bringing that capacity on stream. These companies include major pharmaceutical companies, large generic manufacturers and specialty chemical producers. Roche is now actively engaged in discussions about technology transfers and commercial terms with this shortlist of companies.

“The skills of the different companies offering their services have been thoroughly evaluated by our technical team in recent weeks. As we have surveyed the applications we have focused our attention on how our specialist production team together with each contributing company can further advance global supply,” commented Jan van Koeveringe, Head of Pharma Global Technical Operations.

Roche now shifts its emphasis and resources to technical transfer and implementation. Therefore the formal process for new contacts has been closed.

Roche’s expanded capacity – delivery dates brought forward
Roche recently announced that it will have increased its own production capacity with existing partners and be in a position to produce 300 million treatments of Tamiflu annually going into 2007. To date all government orders for pandemic supplies have met their agreed delivery dates and with the further stepwise scale-up of its production network activated mid- 2006 Roche will be in a position to bring forward delivery timelines.

Roche’s efforts to support government pandemic stockpiling
Roche has been working with many governments over the last few years to determine their needs for stockpiling of Tamiflu and has received and/or fulfilled orders from around 50 countries. In specific countries, particularly in South East Asia , in light of their close proximity to the outbreaks of “bird flu” the company has been in a position to advance delivery schedules. This includes:

-         Taiwan , where Roche will be in a position to deliver requested quantities during 2006

-         Vietnam , where Roche will be providing capsules or active pharmaceutical ingredient for  third parties to encapsulate locally

-         Korea and Malaysia where Roche are providing capsules

-         In India where Roche will be delivering 100,000 treatment courses of Tamiflu ordered by the Indian Government and where negotiations about a local sub-licence are ongoing with local manufacturers.

In Thailand , Philippines and Indonesia , Tamiflu is not patent protected. These governments are therefore free to purchase or manufacture oseltamivir at their discretion. Roche remains willing to discuss supplying governments’ orders and the quality requirements of supply.

Patent and Pricing
Tamiflu exists through innovation as a result of the patent system and it is important that medical innovation continues to be encouraged through the granting of patents. Through its collaboration and use of sub licence policy, Roche contributes to the defense against a potential influenza pandemic while also defending intellectual property rights - the key incentive for future innovation.

In addition, Roche offers a tiered pricing system for the sale of Tamiflu with significant reductions for pandemic use. These lower prices are further reduced for less developed countries.

Roche and WHO
Roche has also pledged to donate 3 million Tamiflu treatments to the WHO as a rapid response stockpile for use at the epicentre of a pandemic. This amount, according to experts, could contain or slow down the spread of a potential pandemic at the source of the outbreak, if delivered rapidly. Roche continues to collaborate with WHO as they prepare for the “Donor Conference” in January 2006.

In Summary
“The supply chain now being put in place exceeds our current orders from World Governments. During 2006 our supply chain will grow dramatically reaching an annualized 300 million plus treatments by the start of 2007. We are now also in the position to have a back-up supply in case of an emergency and specific geographic coverage has also been enhanced with suppliers in Europe , the Americas and Asia . Companies we identified to take the capacity further will therefore allow Roche’s supply network to respond to future demands from world governments,” concluded David Reddy, Roche Pandemic Task Force Leader.

Roche and Gilead
Tamiflu was discovered by Gilead and developed jointly by Gilead and Roche. Roche has exclusive world-wide rights for the manufacturing and marketing of Tamiflu and continues to work in partnership with Gilead .

 

Roche announces further progress in Tamiflu (oseltamivir) production expansion Roche’s current production network on track to produce 300 million treatments as of 2007 Over 150 requests received from third parties - first negotiations initiated .

Roche has announced that it will have increased its own production capacity by the end of 2006 to then be in a position to produce 300 million treatments of Tamiflu annually. The expansion will be achieved by a further stepwise scale-up of Roche’s production network. It means a ten fold increase over the capacity in 2004 when the decision was taken to increase production, without any firm pandemic orders in place, in order to meet the international needs for pandemic planning.

William M. Burns, CEO Division Roche Pharma, commented: “Patients’ needs in case of a pandemic remain our top priority. We have continually increased our production capacities and are now putting in place the means to increase production of Tamiflu to 300 million treatments as of 2007. In addition, we have entered into discussions with a number of interested parties to expand world wide supply, so governments can be as prepared as possible if the influenza pandemic happens.”

More than 150 requests from third parties have been received to date and Roche production experts have already been in initial talks with 8 companies, amongst them large generic manufacturers and major pharmaceutical companies, as well as with a number of governments, including Taiwan and Vietnam . The goal is to be in a position to select potential partners for more detailed discussions by the end of November. Selection criteria are quality, technical ability, capacity and the speed of bringing that capacity on stream.

About pandemic planning
Roche has been working with many governments over the last few years to determine their needs for stockpiling of Tamiflu and has received and/or fulfilled orders from around 50 countries.

Roche has also pledged to donate 3 million treatments to the WHO for use where an influenza pandemic may start. This amount, according to some experts, could contain or stop the spread of a potential pandemic at the source of the outbreak, if delivered rapidly.

Recently Roche has donated Tamiflu to Turkey and Romania , following the emergence of the avian influenza virus in these countries

About Tamiflu (oseltamivir)

Tamiflu is designed to be active against all clinically relevant influenza viruses and key international research groups have demonstrated, using animal models of influenza that Tamiflu is effective against the avian H5N1 strain circulating in the Far East.³

It 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.

Tamiflu delivers:

·         38 percent reduction in the severity of symptoms[i]

·         67 percent reduction in secondary complications such as bronchitis, pneumonia and sinusitis in otherwise healthy individuals [ii]

·         37 percent reduction in the duration of influenza illness^{5, [iii]}

·         Tamiflu was shown to provide up to 89 percent overall protective efficacy against clinical influenza in adults and adolescents who had been in close contact with influenza-infected patients[iv]

In children, Tamiflu delivers:

·         36 percent reduction in the severity and duration of influenza symptoms[v]

·         44 percent reduced incidence of associated otitis media as compared to standard care[vi]

As with any antiviral, a theoretical potential exists for an influenza virus to emerge with decreased sensitivity to a drug. Extensive monitoring, by Roche and the independently established Neuraminidase Inhibitor Susceptibility Network (NISN) measured the incidence of resistance to NAIs. From around 4000 patients treated with Tamiflu resistance was encountered in 0.4 per cent in adults and 4 per cent in children aged one to 12. This resistant virus was found to be less virulent than the wild type virus and did not affect the course of the illness.

The greatest use of Tamiflu today is in Japan . To illustrate this, there were an estimated 16 million influenza infections in Japan over the 2004/2005 influenza season. Roche estimates that around 6 million of those individuals infected with the influenza virus received Tamiflu. Even with this degree of usage, resistance appears very infrequent.

Avian Influenza and Pandemics

Most avian influenza viruses are not infectious to humans, but, should an avian and a human influenza virus co-infect a human or a pig, the virus strains can join, mutate and create a completely new virus, which may be transmissible from animals to humans, and from humans to humans. Such a strain would be entirely new in composition, so vaccines developed and administered to date to protect humans during seasonal epidemics, might be ineffective against this new strain, leaving the population vulnerable to infection. Experts believe the next influenza pandemic could result from such a mutation of virus strains.

World Health Organisation

The WHO has recommended as part of its Pandemic Preparedness Plan that countries establish stockpiles of antiviral treatments such as Tamiflu, which are effective against all strains of the influenza virus. The Pandemic Preparedness Plan, along with details of the 15 countries that have implemented national plans, can be viewed at: http://www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_EDC_99_1/en/