TRIZIVIR^TM APPROVED BY HEALTH CANADA - FIRST TO COMBINE THREE HIV MEDICATIONS IN ONE TABLET

Reduction in pill burden simplifies therapy, improves adherence

Montreal, Quebec - November 6, 2001 - GlaxoSmithKline Inc. and Shire BioChem Inc. announced today that the Therapeutic Products Directorate (TPD) of Health Canada has approved Trizivir^TM, the first and only HIV triple combination antiretroviral therapy in a single tablet, in Canada. Trizivir combines the three active ingredients of the widely used HIV medications 3TC® (lamivudine), Retrovir® (zidovudine/AZTT) and Ziagen® (abacavir sulfate).

Recently released data from a 48 week study¹ demonstrated Trizivir's significant improvement in patient adherence and tolerability with an equivalent efficacy compared to a protease inhibitor (PI)-based regimen. Moreover, data up to 104 weeks ² shows that Trizivir provides long-term suppression of HIV. Taken as a single tablet two times a day, Trizivir provides a more manageable treatment option for people living with HIV/AIDS requiring highly active antiretroviral therapy (HAART). Trizivir is now available across Canada by prescription only.

"Improving patient adherence to complex drug regimens such as those for HIV/AIDS is an important clinical advance," said Dr. Sharon Walmsley, Associate Professor of Medicine, University of Toronto and Assistant Director, Immunodeficiency Clinic, Toronto General Hospital. "In this regard, Trizivir is a meaningful step towards simplifying antiretroviral therapy regimens for people living with HIV," she added.

Trizivir can be taken alone or in combination with other antiretroviral agents for the treatment of HIV infection. The individual components of Trizivir will continue to be available. 3TC and Retrovir are also already available in a dual combination product called Combivir®.

On average, people being treated for HIV take as many as 12 tablets or capsules per day just to treat their HIV. This does not include vitamins or medications for other conditions. Some of the HIV medications people are required to take may have food and fluid restrictions or requirements, or require complicated multiple dosings throughout the day. Trizivir does not have any food or fluid restrictions, and does reduce overall pill burden.

"Many of us who live with HIV have become frustrated with managing complex treatment regimens. As long as they are tailored to individual needs, new options that are simpler and easier to manage would be most welcome," said Ron Rosenes, Honourary Director, AIDS Committee of Toronto.

"The introduction of Trizivir is an important advance in the treatment of HIV/AIDS," said Dr. Anne Phillips, Vice President of Research and Development, GlaxoSmithKline Inc. "With no food or fluid restrictions or requirements, and a smaller pill burden, Trizivir will help many HIV/AIDS patients to simplify their often difficult and complex HIV therapy and should be considered as a potent option for people recently diagnosed."

"This regimen is intended to simplify treatment through less pills," said Joseph Rus, President and CEO, Shire BioChem. "Reducing pill burden - a key challenge in managing the treatment of HIV infection - may thereby improve adherence."

REQUIP

ReQuip is indicated for the treatment of the signs and symptoms of idiopathic Parkinson's Disease. ReQuip is a second-generation D2/D3 dopamine agonist and is generally well tolerated. The most commonly reported side effects associated with early therapy in clinical trials were nausea, dizziness, somnolence, headache, peripheral edema, vomiting, syncope, fatigue and viral infection. As adjunct therapy in clinical trials, the most commonly reported side effects were: dyskinesia, nausea, dizziness, somnolence and headache.

Studies demonstrate adherence, tolerability

In 48 week study data¹ released at the recent 1st International AIDS Society Conference on HIV Pathogenesis and Treatment, 72 per cent of patients taking a combination of Ziagen + Combivir, the active ingredients in Trizivir, showed greater than 95 per cent adherence, compared to 45 per cent of those taking a regimen of the combination indinavir + Combivir (p<0.001). Ziagen + Combivir has demonstrated fewer drug-related adverse events than the combination of Combivir/indinavir (65 per cent and 87 per cent respectively; p<0.001). Moreover, the study found the Ziagen + Combivir arm to be statistically superior (p=0.002), with 66 per cent of patients achieving a level of virus under 400 copies/ml, compared to only 50 per cent of patients taking the PI-based regimen.

In another study², Trizivir was found to be generally well tolerated even after two years of therapy. Additionally, a further study³ revealed that at 48 weeks of treatment, total cholesterol increase was significantly lower with Trizivir and fewer manifestations of lipid abnormalities were observed when compared to a PI-based regimen.

A hypersensitivity reaction has been associated with abacavir. This hypersensitivity reaction can be life threatening. Patients experiencing symptoms of this reaction should stop taking Trizivir or Ziagen and contact their physician immediately. During the clinical trial program, hypersensitivity reaction has been observed in approximately four per cent of patients. Patients who have previously experienced a hypersensitivity reaction to abacavir must never use a product containing abacavir again, including Ziagen and Trizivir.

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. In Canada, GlaxoSmithKline employs approximately 1,800 people who work to discover, develop, manufacture and market new medicines for the treatment of migraine, asthma, HIV/AIDS and other infectious diseases, cancer, depression, and diabetes. The company is a top 20 investor in Canadian research and development, contributing more than $100 million annually. It is also one of the top 10 corporate charitable donors, investing more than $6.5 million annually.

Shire BioChem is part of one of the world's leading and fastest growing specialty pharmaceutical companies - the Shire Pharmaceuticals Group plc (Shire). With operations in key markets worldwide, Shire has a strategic focus on three therapeutic areas - central nervous system (CNS) disorders, oncology and anti-infectives. Shire also has leading expertise in advanced drug delivery and biologics. The Group has a global sales and marketing infrastructure with a broad portfolio of products and its own direct marketing capability in the US, Canada, the UK, the Republic of Ireland, France, Germany, Italy and Spain, with plans to add Japan. The Canadian Shire operation is known under the name, Shire BioChem Inc., and incorporates the Canadian sales and marketing function. Two other Shire businesses that are located in Canada are Shire Biologics and CADx Medical Systems. Some global corporate functions for the Shire group also operate out of Laval. Shire now has some 440 employees in Canada, with facilities located in Laval, Quebec, near Montreal and in Sainte-Foy, Quebec, near Quebec City. Shire BioChem was created following the merger of BioChem Pharma with Shire in May 2001.

FOR MORE INFORMATION, PLEASE CONTACT:

Sylvie Tessier

GlaxoSmithKline

(514) 956-3115

Trizivir^TM is a trademark, used under license by GlaxoSmithKline Shire BioChem.

Retrovir® and Ziagen® are registered trademarks, GlaxoSmithKline Inc.

3TC® and Combivir® are registered trademarks, used under license by GlaxoSmithKline Shire BioChem.

References:

1. Vibhagool, A, et al. Abacavir plus Combivir® versus indinavir plus Combivir® in antiretroviral therapy-naïve adults: results of a 48-week open label, equivalence trial. Presented at the 1st International AIDS Society Conference on HIV Pathogenesis and Treatment; July 8 - 11, 2001; Buenos Aires, Argentina.
2. Antela A. Long-term (104 week) virologic suppression with triple nucleoside HAART regimen ABC/3TC/ZDV. Presented at the 5th International Congress on Drug Therapy in HIV Infection; Oct. 22-26, 2000; Glasgow, UK.
3. Matheron S, Massip P, Trepo C, et al. Metabolic and clinical evaluation of lipodystrophy syndrome in HIV-1 infected adults receiving initial HAART with or without a protease inhibitor; 48-week data from the CNAF3007 study. Presented at the 8th Conference on Retroviruses and Opportunistic Infections; Feb. 4-8, 2001; Chicago, Illinois.