The European Committee for Human Medicinal Products (CHMP) has confirmed that the presence of an impurity called ethyl methanesulfonate (EMS) in Roche’s Viracept (nelfinavir mesylate) did not increase patients’ risk of developing cancer.

The discovery of the EMS impurity in some batches of Viracept led to a global recall of this HIV medication in June 2007. Since then, the product has been made available again in the EU.

The conclusions announced today were based on tests with EMS, which have been validated by independent experts including toxicologists and HIV-treating clinicians. The results were also reviewed by patient advocates and non-governmental organizations.

“Roche has acted promptly and responsibly in generating this new research on EMS” said Dr Anton Pozniak, Consultant Physician in HIV, Chelsea and Westminster Hospital, London, UK. “The results of the studies – validated by a panel of independent toxicologists and clinicians – as well as the conclusions of the CHMP should provide reassurance to patients who were exposed to elevated levels of EMS, and to their healthcare providers.”

In collaboration with the CHMP, Roche designed and commissioned in-depth animal studies to better define the potential impact of EMS. These studies demonstrated that patients who were accidentally exposed to the highest levels of EMS in Viracept received doses of the impurity significantly below the threshold at which DNA damage – and therefore cancer or birth defects – can occur.

“Our primary focus throughout this process has been on protecting the safety of patients” said William M. Burns, CEO, Roche Pharmaceuticals Division. “Roche undertook this important research because so little was known about EMS at the time the recall was initiated. We welcome the CHMP’s conclusions and expect that the rapid generation and dissemination of the data will make an important contribution to the industry as a whole.”

The full data will be shared with the broader HIV and research communities via scientific conferences and peer-reviewed journals in the coming months. An initial presentation has been accepted as late-breaker poster at the XVII International AIDS Conference, 3-8 August, 2008.

Additionally, Roche had initiated the first steps to establish patient registries as part of its efforts to monitor and track patients who may have been exposed to contaminated batches of Viracept. However, in light of the new research, the CHMP has concluded that there is no need to follow these patients in registries.

Following the discovery of elevated levels of EMS in some batches of Viracept, Roche in June 2007 undertook a total global recall in areas of the world where it supplies the drug. This was followed by the suspension of Viracept’s license in August 2007. In agreement with the CHMP, Roche undertook a comprehensive review and correction of its manufacturing procedures, which led to Viracept’s licence being reinstated in October 2007.

About Viracept

Viracept (nelfinavir) is an HIV protease inhibitor supplied by Roche outside the US, Canada and Japan. Viracept was first introduced by Roche in 1998. Although newer protease inhibitors have become available for the treatment of HIV, it is viewed as a useful medicine for patients who are intolerant to ritonavir (since it does not require ritonavir boosting), pregnant women, and patients in resource-limited settings, since the formulation is heat-stable and does not require refrigeration.

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, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, 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 Swiss 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 79,000 people. Additional information is available on the Internet at www.roche.com.

All trademarks used or mentioned in this release are protected by law.

Contacts:

Mike Nelson, Roche

+41 (79) 572 5165

Dafni Kokkidi,

Ketchum

+44 (0)20 7611 3591

Studies emphasize lack of cancer risk for patients exposed to this impurity in Viracept

New data from studies presented at the XVII International AIDS Conference in Mexico City have provided unprecedented insight into the toxicity of an impurity called ethyl methanesulfonate (EMS). The formation of the EMS impurity is a potential by-product of the manufacturing of mesylate salts, which are contained in over 40 drugs currently available worldwide.

The studies were designed to determine the impact of elevated EMS levels in some batches of Roche’s Viracept® (nelfinavir mesylate) and demonstrated a clear threshold response at which DNA damage, the underlying mechanism for the carcinogenesis of EMS, occurs. The results of these animal studies, which can be translated to humans with high confidence, confirm that Viracept patients exposed to the EMS impurity at levels well below this threshold are not at an increased risk of cancer.

“These data provide unprecedented insight into the toxicity of EMS for humans. They will change the long held perceptions of the hazards posed by low doses of some genotoxic carcinogens”, said Professor David Tweats, Department of Medicine and Genetics, University of Wales Swansea, UK.

EMS is a known DNA-damaging agent capable of inducing gene mutations and chromosomal aberrations. Although existing in vitro data indicated that there was a threshold response at lower doses of EMS¹ at which no DNA damage was observed, the total body of literature about EMS at low doses was limited.  Consequently, available data did not permit an adequate risk assessment for patients exposed to EMS in Viracept. Roche -- in agreement with the European regulatory agency -- undertook the largest and most comprehensive toxicology evaluation of EMS to-date.

Scientists investigated the genetic toxicity of EMS using the following sets of studies:

• Measurement of chromosomal damage in mice

• Quantification of gene mutations in the transgenic MutaMouse model - the largest study of its kind ever conducted

•  Modelling of exposure and metabolism of EMS in humans based on experimental animal data

The first study clearly demonstrated a threshold-dose response with no chromosomal damage at EMS doses up to and including, 80 mg/kg/day. The second set of studies, the transgenic MutaMouse studies, also showed a clear threshold effect for mutations above 25 mg/kg/day, under chronic conditions. Effects were also shown not to be cumulative over time. This threshold is far above 0.055 mg/kg/day -- the highest estimated levels to which Viracept patients were exposed for no longer than 3-6 months.

The research team used these results to predict human exposure to EMS. They predicted that even at a maximal exposure level 370-fold higher than that calculated for affected Viracept patients, the damage potentially incurred by EMS can still effectively be dealt with by ubiquitous DNA repair mechanisms.  As chromosome damage and mutations are the underlying molecular events for birth defects and cancer, the results of these studies can be used to reassure patients exposed to elevated levels of EMS, and their healthcare providers, that they are not at increased risk for developing cancer.

Notes to editor

Following the discovery of elevated levels of EMS in some batches of Viracept, Roche in June 2007 undertook a total global recall in areas of the world where it supplies the drug. This was followed by the suspension of Viracept’s license in August 2007. In agreement with the European health authority, Roche undertook a comprehensive review and correction of its manufacturing procedures, which led to Viracept’s licence being reinstated by the European Commission in October 2007. Since then, the product has been made available again in the EU.

About Viracept

Viracept (nelfinavir) is an HIV protease inhibitor supplied by Roche outside the US, Canada and Japan. Viracept was first introduced by Roche in 1998. Although newer protease inhibitors have become available for the treatment of HIV, it is viewed as a useful medicine for patients who are intolerant to ritonavir (since it does not require ritonavir boosting), pregnant women, and patients in resource-limited settings, since the formulation is heat-stable and does not require refrigeration.

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 www.roche.com.

All trademarks used or mentioned in this release are protected by law.

Contacts:

Mike Nelson, Roche

+41 (79) 572 5165

Sébastien Desprez, Ketchum

+44 (0) 776 823 8289 (onsite at IAC)

+44 (0) 207 611 3522

Free of charge expertise for factories in Bangladesh, Kenya, Tanzania and Zimbabwe

Roche today announced that it has entered into four new technology transfers with local manufacturing companies in Africa and Asia; Regal Pharmaceuticals in Kenya, CAPS Holdings in Zimbabwe, Shelys Pharmaceuticals in Tanzania and Beximco Pharmaceuticals Ltd in Bangladesh. As part of Roche's Technology Transfer Initiative, these companies will be provided free of charge with the technical expertise to manufacture generic HIV medicine, based upon the processes to produce saquinavir, Roche's 2nd line¹ HIV medicine.

Since its launch two years ago, Roche has signed Technology Transfer agreements with a total of nine companies across sub-Saharan Africa and the world's Least Developed Countries. Furthermore Roche has received expressions of interest from a total of 35 manufacturers in 15 eligible countries, including Kenya, Ghana, Zimbabwe and Nigeria. Roche will continue to work with these individual applicants to assess production capabilities.

William M. Burns, CEO Division Roche Pharma, said: "These new agreements highlight the ongoing contribution that our Technology Transfer Initiative is making to help strengthen and expand local manufacturing capabilities for HIV medicines in resource-limited countries. With more local manufacturers now looking to scale-up production of essential medicines, the continued uptake of this initiative highlights Roche as an innovative leader in supporting sustainable solutions to improve HIV healthcare where it is needed most."

In addition to these four new agreements, Roche has expanded the Technology Transfer Initiative with training seminars for local manufacturers across sub-Saharan Africa and the world's Least Developed Countries. These sessions focus on the development of improved manufacturing processes and provide a forum for Roche to share its knowledge and experience with those who have access to fewer resources. The knowledge gained by local manufacturers enables them to strengthen their manufacturing capability, increase manufacturing knowledge on the production of medicines beyond HIV.

Rahul Malhotra, General Manager GMP & Formulations, Shelys Pharmaceuticals, Tanzania commented: "The practical support that Roche has provided has been a great learning experience for my team, enabling us to make improvements to our entire technical and quality systems. We have been enthused by this partnership and are eager to work with Roche on this initiative to help meet the needs of our people suffering from HIV infections, and improve availability of these badly needed medications."

Roche's dedicated team will work onsite at manufacturing facilities at all four locations and from its headquarters in Switzerland to undertake the technology transfers. The companies will be able to produce saquinavir for supply throughout countries in sub-Saharan Africa, and to those defined as Least Developed by the United Nations, due to Roche's policy of not filing patents on antiretroviral medicines in these countries.

About Roche's Technology Transfer Initiative

Announced in January 2006, the Roche Technology Transfer Initiative aims to provide local manufacturers with the technical expertise required to produce generic HIV medicines. Manufacturers in sub-Saharan Africa and the Least Developed Countries wishing to produce generic saquinavir for use in these countries will not be required to apply for a voluntary licence, as Roche has committed as part of its global policy not to enforce patents on antiretroviral medicines within these countries. Interested manufacturers should contact the Project Manager, Technology Transfer Initiative at the Roche Kenya office: info.aidstechtransfer@roche.com.

Interested local manufacturers in the following countries are invited to contact Roche to discuss the Technology Transfer Initiative: Afghanistan, Angola, Bangladesh, Benin, Bhutan, Burkina Faso, Botswana, Burundi, Cambodia, Cameroon, Congo, Côte d'Ivoire, Cape Verde, Central African Republic, Chad Comoros, Democratic Republic of Congo, Djibouti, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Ghana, Gambia, Guinea, Guinea-Bissau, Haiti, Kenya, Kiribati, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Maldives, Mali, Mauritius, Mauritania, Mozambique, Myanmar, Namibia, Nigeria, Nepal, Niger, Rwanda, Samoa, Sao Tome and Principe, Seychelles, Senegal, Sierra Leone, Solomon Islands, Somalia, South Africa, Swaziland, United Republic of Tanzania, Timor-Leste, Togo, Tuvalu, Uganda, Vanuatu, Yemen, Zambia, Zimbabwe.

About Roche's patent and pricing policy

In addition to its Technology Transfer Initiative, Roche will maintain its current pricing and patent policy. No patents for any of Roche medicines - across all disease areas - will be filed in the world's Least Developed Countries (LDCs), as defined by the UN. Roche will not file patents on new antiretroviral medicines in LDCs or sub-Saharan Africa. Roche will not take action in these countries against the sale or manufacture of generic versions of antiretroviral medicines. Generic versions of such HIV medicines can therefore be produced in LDCs and sub-Saharan Africa without the need for a voluntary or compulsory licence. Roche makes its HIV protease inhibitors Invirase and Viracept available at no profit prices for direct supplies from Roche Basel to LDCs and sub-Saharan Africa.

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, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolic disorders and diseases of the central nervous system. In 2006 sales by the Pharmaceuticals Division totaled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invests approximately 7 billion Swiss francs a year in R&D. Worldwide, the Group employs about 75,000 people. For further information, please visit www.roche.com .

All trademarks used or mentioned in this release are protected by law.

Additional information

- Roche & HIV/AIDS: www.roche-hiv.com
- Access to Roche's medicines: www.roche.com/sus_med.htm

¹ WHO treatment guidelines for resource limited settings: http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf

Roche Group Media Relations

Phone: +41 61 688 8888 / e-mail: basel.mediaoffice@roche.com
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