Media Release

Basel, 19 September 2005

Once-monthly oral Bonviva approved for postmenopausal osteoporosis in Europe

Highly effective single monthly tablet a first for any chronic disease

Roche and GlaxoSmithKline (GSK) today announced that European Union marketing authorization has been granted for Bonviva 150mg for the treatment of postmenopausal osteoporosis. Bonviva (ibandronic acid) is the first and only once-monthly tablet for the treatment of postmenopausal osteoporosis. This announcement follows FDA and Swissmedic approval earlier this year. Bonviva, a potent and highly effective bisphosphonate1 is the first ever oral treatment administered as one tablet once a month for any disease. This means patients will only have to take 12 Bonviva tablets a year versus 52 or 365 required with current weekly or daily bisphosphonate treatments. This is particularly important as many patients find osteoporosis therapy inconvenient, which may help to explain why up to two-thirds of patients stop taking their osteoporosis treatment within a year,2 foregoing the bone building benefits these drugs can only provide over time.3

Poor adherence has a negative effect on treatment outcomes including lower gains in bone mineral density (BMD),4,5 smaller decreases in the rate of bone turnover4 and a significantly greater risk of fractures6

William M. Burns, CEO Division Roche Pharma said: “We are very pleased about the European Union marketing authorization for once-monthly Bonviva. We can now offer women with postmenopausal osteoporosis an effective and more convenient regimen which could help them stay on therapy, therefore providing the bone-building benefits they need over time”.

Andrew Witty, President of EU Pharma, GSK said: “GSK welcomes this announcement and is delighted to be able to offer healthcare professionals and patients throughout Europe a once monthly treatment option for postmenopausal osteoporosis”.
Bonviva, a highly effective bisphosphonate, delivered a reduction in the occurrence of new vertebral fractures of 62% over three years at a 2.5mg daily dose.7 Bonviva is also the only nitrogen-containing bisphosphonate that has demonstrated a reduction in vertebral fracture risk using a drug-free interval of more than one day.7

European Union marketing authorization for once monthly oral Bonviva is based on 2-year results of the MOBILE (Monthly Oral iBandronate In LadiEs) phase III study in 1,609 women with postmenopausal osteoporosis. The study shows the monthly dose was highly effective and well tolerated over two years and is actually statistically superior at increasing bone mineral density (BMD) compared to the daily dose.1

Bonviva (known in the US as Boniva) 150mg once-monthly oral is indicated for the treatment of postmenopausal osteoporosis in Europe. It is anticipated the UK and Germany will be first to launch the once-monthly formulation in the EU. In the US, once-monthly Boniva 150mg is indicated for the treatment of osteoporosis in postmenopausal women. In the USA and in Europe, Bonviva is co-promoted by GSK.

About MOBILE
MOBILE (Monthly Oral iBandronate In LadiEs) is a two-year, randomized, double-blind trial comparing the efficacy and safety of monthly oral doses of ibandronate (100mg on a single day; 100mg as separate 50mg doses on two consecutive days; or 150mg on a single day) versus the oral daily regimen (2.5mg), approved by the FDA and European Commission, in 1,609 women with postmenopausal osteoporosis. The primary endpoint was analysed at 1 year. One year results from MOBILE were recently published in the Journal of Bone and Mineral Research4 and full two year results were presented at the Annual European Congress of Rheumatology, Vienna, Austria 8-11 June 2005.1

About Bonviva
• Bonviva, a potent bisphosphonate, has been studied to date in clinical trials involving over 12,000 patients
• The ongoing clinical development programme is evaluating monthly oral and bi-monthly/quarterly intravenous dosage regimens in women with postmenopausal osteoporosis
• Once-daily Bonviva is indicated for the treatment and prevention of osteoporosis in postmenopausal women by reduction of elevated bone turnover, increasing bone mineral density and reduction of the incidence of vertebral fractures
• Studies specifically designed to demonstrate reductions in non-vertebral or femoral neck fractures have not been conducted with Bonviva
• Bonviva, like other bisphosphonates administered orally, may cause upper gastrointestinal disorders such as dysphagia, oesophagitis and oesophageal or gastric ulcer
• Bonviva (known in the US as Boniva), was approved by the US Food and Drug Administration in March 2005. In the US, Boniva 150mg is indicated for the treatment of osteoporosis in postmenopausal women.

Roche/GSK collaboration
In December 2001, F. Hoffmann-La Roche (Roche) and GlaxoSmithKline (GSK) announced their plans to co-develop and co-promote Bonviva for the treatment and prevention of postmenopausal osteoporosis in all countries except Japan. The Roche/GSK collaboration provides expertise and commitment to bringing new osteoporosis therapies to market as quickly as possible.

About GSK
GSK, 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. For company information, visit GSK on the Internet at www.gsk.com.

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 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’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. For further information: www.roche.com.

All trademarks used or mentioned in this release are legally protected.




Additional information
- About postmenopausal osteoporosis
- Roche Health-Kiosk, Osteoporosis


References:
1. Cooper C, Delmas PD, Felsenburg D, Hughes C, Mairon N et al. Two-year efficacy and tolerability of once monthly oral ibandronate in postmenopausal osteoporosis: the MOBILE study. Abstract presented at the Annual European Congress of Rheumatology, Vienna, Austria 8-11June 2005.
2. DIN-LINK data, Compufile Ltd, January 2004. NB. Patients are excluded from the analysis at the point where they stop taking therapy altogether or have failed to comply fully.
3. Sebaldt R, Shane L, Pham B, et al. Impact of non-compliance and non-persistence with daily bisphosphonates on longer-term effectiveness outcomes in patients with osteoporosis treated in tertiary specialist care. J Bone Miner Res 2004;19(Suppl. 1): (Abstract M423).
4. Eastell R et al. Calcif Tissue Int 2003;72:408 (Abstract P-297)
5. Finigan J et al. Osteoporos Int 2001;12:S48–S49 (Abstract P110)
6. Caro J et al. Value Health 2002;5:127
7. Chestnut et al. Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis. Journal of Bone & Mineral Research, vol. 10: 8, 2004.