Today Shire plc announced the launch of FOSRENOL® (lanthanum carbonate) in the United Kingdom following the product's authorisation as a phosphate binding agent for use in the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

FOSRENOL is an effective non-calcium phosphate binder, which maintains control of phosphate levels,1 and is well-tolerated in the majority of patients. FOSRENOL provides a new option for the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or CAPD, and most patients can be managed with one chewable tablet during each meal.2

It is estimated that over 23,000 patients in the UK currently have end stage renal disease (ESRD)3, approximately 70 per cent of these patients have hyperphosphataemia4 (abnormally high phosphate levels).

If it is not managed successfully, hyperphosphataemia can cause serious long-term health risks leading to renal osteodystrophy (resulting in bone pain, brittle bones and skeletal deformities)5 and potentially contributing to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients.6,7

Dr Alastair Hutchison from the Manchester Institute of Nephrology & Transplantation welcomed the news of FOSRENOL's launch into the UK and explained: "Control of hyperphosphataemia remains an unmet clinical need in many patients with CKD, with many still having phosphate levels well above the recommended limit. The introduction of FOSRENOL to the UK provides patients with a new, effective therapy that is easy and convenient to take, helping to simplify their control of phosphate levels."

At the end of 2006 the National Kidney Federation (NKF) concluded a survey of over 2,000 of its members to gain an understanding about how CKD patients deal with the condition on a daily basis.8 Dr. Steve Riley, Institute of Nephrology, University Hospital of Wales made the following conclusions based on the NKF data:

-- Patients with CKD have a poor understanding of the consequences of hyperphosphataemia8

-- One quarter of dialysis patients reported problems taking their phosphate binders and around one third reported missing phosphate doses at least once a week8

-- 26 per cent of patients believed that taking fewer pills to manage serum phosphate levels would result in increased levels of adherence to phosphate-binder therapy8.

Dr Riley said of the results: "Some patients in the NKF survey felt that the high tablet burden of existing phosphate binders was a significant challenge to adherence. Therefore, improving choice by the introduction of new and effective phosphate binders which have a lower tablet burden may help to improve patient adherence."

Many people find it difficult to take phosphate binders over the long-term because of the high doses and high numbers of tablets (up to twelve per day) that have to be taken. FOSRENOL enables a reduction in tablet burden, allowing most patients to take just one tablet per meal, while providing an equivalent level of phosphate control.9

Over 5,000 patients have been treated with FOSRENOL during an extensive worldwide clinical research programme.10 The UK launch of FOSRENOL increases the treatment options for hyperphosphataemia since its introduction to the United States in January 2005. FOSRENOL is also available in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Iceland, Ireland, The Netherlands, Poland and Sweden.

John Freeman, Managing Director, Shire UK said, "Shire is delighted to launch FOSRENOL in the UK where effective control of serum phosphate levels is seen as complex and challenging for patients with CKD, many of whom have to take numerous tablets with each meal to control their phosphate. FOSRENOL provides a new treatment option for patients helping them simplify their management of hyperphosphataemia".

Hyperphosphataemia occurs in approximately 70% of patients with ESRD4. Phosphate enters the body through the normal daily diet, and due to the body's reduced ability to excrete phosphate, serum phosphate levels rise leading to hyperphosphateamia. Dialysis patients are on a challenging and unpalatable low phosphate diet to help with this issue, and although dialysis itself attempts to address this imbalance, many patients receiving dialysis have serum phosphate levels exceeding 2.1 mmol/L (6.5 mg/dl), far beyond the current UK Renal Association Guideline upper limit of 1.8mmol/L.11 Phosphate binder therapy is therefore important to achieve phosphate control.

Despite the availability of several phosphate binders, effective phosphate management remains a challenge. The launch of FOSRENOL in the UK will provide physicians with a new treatment option for the management of hyperphosphataemia in their patients with CKD on haemodialysis or CAPD, with most patients being managed with just one tablet during each meal.

References:

1. Hutchison AJ et al. Long-term efficacy and tolerability of lanthanum carbonate: results from a 3-year study. Nephron Clin Pract 2006;102(2): c61-71.
2. FOSRENOL® Summary of Product Characteristics. January 2007.
3. The Renal Association. UK Renal Registry, Eighth Annual Report. December 2005, p39,p40,p41. Link here Accessed on 5 Feb 2007.
4. Albaaj F, Hutchison AJ. Lantham Carabonate for the Treatment of Hyperphosphataemia in Renal Failure and Dialysis Patients. Expert Opin. Pharmacother 2005; 6(2): 319-328.
5. Martin K, Gonzalez A. Strategies to minimize bone disease in renal failure. Am J Kidney Dis 2001; 38: 1430-36
6. Salusky IB et al. Cardiovascular calcification in end-stage renal disease. Nephrol Dial Transplant 2002; 17: 336-339.
7. Block G et al. Re-evaluation of risks associated with hyperphosphataemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. Am J Kidney Dis 2000; 35 (6): 1226-1237.
8. Riley S. Patient perceptions of phosphate binders - Results of a patient questionnaire. Data on file. 08.2589
9. Vemuri N et al. Lanthanum carbonate provides serum phosphorus control with a reduced tablet burden. Poster presented at ERA/EDTA, Glasgow 15-18 July 2006.
10. Shire Data on File 08.2644
11. The Renal Association. UK Renal Registry, Eighth Annual Report. December 2005,

p149. Managing Hyperphosphataemia

Phosphorus, an element found in nearly all foods, is absorbed from the gastrointestinal tract into the blood stream. When the kidneys fail, they no longer effectively filter out phosphates, even with the help of blood-cleansing dialysis machines. While the normal adult range for phosphorus is 2.5 (0.8mmol/L) to 4.5 mg/dL (1.4mmol/L), the blood phosphorus levels of many patients on dialysis exceed 6.5 mg/dL (2.1mmol/L). Such levels have been linked to a significantly higher illness and death risk for patients who have undergone at least one year of dialysis[i]. 70% of patients develop hyperphosphataemia4.

Hyperphosphataemia disrupts the delicate interplay between the body's levels of calcium, parathyroid hormone (PTH) and vitamin D. Over time, hyperphosphataemia can ultimately lead to calcification of the heart, lung and some arteries[ii]. Accumulating evidence shows that hyperphosphataemia contributes to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients[iii]. Studies have shown that cardiovascular mortality in dialysis patients aged 25-34 years is more than 5 times greater than that in people aged 65-74 in the general population[iv].

Since dialysis and diet restrictions alone generally cannot control phosphate levels, patients traditionally manage hyperphosphataemia by taking phosphate binding agents with every meal and snack. Such binders "soak up" phosphate in the gastrointestinal tract, before it can be absorbed into the blood.

FOSRENOL® (lanthanum carbonate)

FOSRENOL® works by binding to dietary phosphate in the GI tract; once bound, the lanthanum/phosphate complex cannot pass through the intestinal lining into the blood stream and is eliminated from the body. As a consequence, overall phosphate absorption from the diet is decreased significantly. Shire has conducted an extensive worldwide clinical research programme for FOSRENOL involving over 5000 patients10. This programme has demonstrated that FOSRENOL is an effective phosphate binder with a good tolerability profile. FOSRENOL was approved by the FDA in October 2004 and is now available for prescription in the US. In March 2005 regulatory authorities in the EU granted marketing authorization for FOSRENOL in sixteen member states, thus completing the first step in securing marketing approval throughout Europe. FOSRENOL has since been launched in Ireland, Sweden, Finland, Denmark and Austria. The final step in the European process was recently completed resulting in recommendation for approval in the remaining 11 member states. Further roll-outs are underway across the rest of Europe and other countries around the world. The company has out-licensed the rights to develop, market and sell FOSRENOL in Japan to Bayer Yakuhin Ltd.

Patients with renal insufficiency may develop hypocalcaemia. Serum calcium levels should therefore be monitored at regular time intervals for this patient population and appropriate supplements given.

No data are available in patients with severe hepatic impairment. Caution should, therefore, be exercised in these patients, as elimination of absorbed lanthanum may be reduced.

FOSRENOL should not be used during pregnancy.

Patients with acute peptic ulcer, ulcerative colitis, Crohn's disease or bowel obstruction were not included in clinical studies with Fosrenol.

The most commonly reported Adverse Drug Reactions (ADRs) (>1/100, 1/10) are gastrointestinal reactions such as abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea and vomiting. These are minimized by taking FOSRENOL with food and generally abated with time with continued dosing. Hypocalcaemia was the only other commonly reported adverse reaction.

SHIRE PLC

Shire's strategic goal is to become the leading specialty pharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit and hyperactivity disorder (ADHD), human genetic therapies (HGT), gastrointestinal (GI) and renal diseases. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire believes that a carefully selected portfolio of products with a strategically aligned and relatively small-scale sales force will deliver strong results.

Shire's focused strategy is to develop and market products for specialty physicians. Shire's in-licensing, merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.

For further information on Shire, please visit the Company's website: shire.

"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization; the impact of competitive products, including, but not limited to the impact of those on Shire's Attention Deficit and Hyperactivity Disorder (ADHD) franchise; patents, including but not limited to, legal challenges relating to Shire's ADHD franchise; government regulation and approval, including but not limited to the expected product approval dates of SPD503 (guanfacine extended release) (ADHD), SPD465 (extended release triple-bead mixed amphetamine salts) (ADHD), MEZAVANT™ (SPD476) (mesalazine) in Europe, and VYVANSE™ (NRP104) (lisdexamfetamine dimesylate) (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire's and its predecessor registrant Shire Pharmaceuticals Group plc's filings with the Securities and Exchange Commission, particularly Shire plc's Annual Report on Form 10-K for the year ended December 31, 2005.

View drug information on Fosrenol, lanthanum carbonate; Vyvanse.

Tag Cloud