Shires UK Launch Expands Global Reach of Fosrenol

 New Option for Effective Control of Phosphate Levels and Potential to Lower Pill Burden Now Available for Patients With End Stage Renal Disease   

BASINGSTOKE, England, March 5, 2007/CNW/ - Shire plc (LSE: SHP, NASDAQ: SHPGY,  TSX: SHQ). Shire recently announced the launch of Fosrenol (lanthanum  carbonate) in the United Kingdom following the product's successful  approval for the control of hyperphosphataemia in patients with chronic kidney  disease on haemodialysis or continuous ambulatory peritoneal dialysis.      

FOSRENOL provides a new simplified treatment option to the estimated  1.4 million people on dialysis worldwide(1) who are at risk from the serious  consequences of hyperphosphataemia. FOSRENOL is an effective treatment for the control of hyperphosphataemia  in patients with CKD on dialysis.(2) FOSRENOL has a high affinity for  phosphate (in vitro data)(3), and therefore in the patients with CKD FOSRENOL  binds to dietary phosphate to effectively reduce serum phosphorus levels.  FOSRENOL is well tolerated and the majority of patients require just one  chewable tablet taken during each meal.(4)      

Dr David Goldsmith, Consultant Nephrologist at Guy's and St Thomas'  Hospitals in London welcomed news of this launch and explained, "Effective  control of hyperphosphataemia remains a difficult problem for many patients on  dialysis, with many patients still having phosphate levels above the  recommended upper limit of 1.78 mmol/L. The introduction of FOSRENOL in the UK  offers patients a new, effective therapy with the added potential benefit of a  reduced pill burden, which may help to simplify the management of their  phosphate levels."       Over 5,000 patients have been treated with FOSRENOL during an extensive  clinical development programme,(5) with a small number having now received  treatment for up to six years.(6) This launch extends the availability of  FOSRENOL which is now available in Australia, Austria, Belgium, Czech  Republic, Denmark, Finland, France, Germany, Iceland, Ireland, Korea, The  Netherlands, Sweden, Taiwan and the US.      

"Shire is delighted with the introduction of FOSRENOL in the UK adding to  recent successful launches into Germany and France, which have helped to  extend the availability of this important new product across Europe," said  David Milton, Senior Vice President, Shire Renal Business Unit. "Effective  control of serum phosphate levels is seen as complex and challenging for  patients with CKD who are already taking a number of different therapies for  their condition. FOSRENOL provides an effective new treatment option helping  to make control of phosphate levels simpler and easier. We hope the UK launch  will continue to build on the success FOSRENOL has achieved in the US, where  it has already benefited thousands of CKD patients."      

Hyperphosphataemia is an almost inevitable consequence of CKD due to the  inability of failing kidneys to effectively rid the body of excess phosphate  that enters the body during daily dietary intake. If not managed successfully, hyperphosphataemia can cause unpleasant  symptoms such as intense itching and in the long-term patients face serious  health risks including renal osteodystrophy, a bone disorder resulting in  painful, brittle bones that may fracture or lead to deformities.(7) Surveys of  medical records have shown that high phosphate levels are also linked with  cardiovascular disease, which accounts for almost half of all deaths among  dialysis patients.(8)       To help manage their phosphate levels, dialysis patients are restricted  to a low phosphate diet, which can be unpalatable and difficult to  maintain.(9) Whilst dialysis can remove some of the ingested phosphate, it is  insufficient alone for the majority of patients. Indeed, up to 75 per cent of  dialysis patients exceed the Kidney Disease Outcomes Quality Initiative  (K/DOQI) guidelines for phosphate of 1.78 mmol/L (5.5 mg/dL).(10) Phosphate  binder therapy is therefore an important and necessary part of achieving  phosphate control. Despite the availability of existing therapies, effective phosphate  management remains a challenge. FOSRENOL provides physicians with an  alternative treatment option to help effectively manage hyperphosphataemia in  their dialysis patients.   

     References:       1. Grassman A et al. ESRD patients in 2004: global overview of patient  numbers, treatment modalities and associated trends. Nephrol Dial Transplant  2005; 20: 2587-2593.   

     2. Hutchison AJ et al. Long-term efficacy and tolerability of lanthanum  carbonate: results from a 3-Year Study. Nephron Clinical Practice 2006; 102:  61-71.   

     3. Damment SJP, Webster I. The pharmacology of lanthanum carbonate  (FOSRENOL(R)): a novel non-aluminum, non-calcium phosphate binder. Poster  presented at 36th Annual Meeting of the American Society of Nephrology, San  Diego, 14-17 November 2003.   

     4. 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.   

     5. Shire Data on File 08.2644.   

     6. Hutchison A et al on behalf of the SPD405-309 Lanthanum Study Group.  Evidence for the long-term safety and tolerability of lanthanum carbonate.  Poster presented at 38th Annual Meeting of the American Society of Nephrology,  Philadelphia, 8-13 November 2005.   

     7. Martin K, Gonzalez A. Strategies to minimize bone disease in renal  failure. Am J Kidney Dis 2001; 38: 1430-36.   

     8. 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.   

     9. Malluche HH, Monier-Fugere M-C. Hyperphosphataemia: pharmacologic  intervention yesterday, today and tomorrow. Clin Nephrol 2000; 54(4): 309-17.   

     10. Kim J et al. Achievement of proposed NKF-K/DOQI Bone Metabolism and  Disease Guidelines: results from the Dialysis Outcomes and Practice Patterns  Study (DOPPS). J Am Soc Nephrol 2003; 14: 269A.   

Notes to Editors:   
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) with up to 75 per cent of patients  developing hyperphosphataemia(ii).       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(iii). Accumulating evidence shows that hyperphosphataemia  contributes to cardiovascular disease, which accounts for almost half of all  deaths among dialysis patients(iv). 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(v).       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(R) 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 patients(vi), with a small number  followed for up to 6 years.(vii) This programme has demonstrated that FOSRENOL  is an effective phosphate binder with a good tolerability profile for  long-term use. FOSRENOL was approved by the FDA in October 2004. 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 Austria,  Belgium, Czech Republic, Denmark, Finland, France, Germany, Iceland, Ireland,  The Netherlands, Poland and Sweden. 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) ((greater  than)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:  http://www.shire.com.   

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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(TM) (SPD476) (mesalazine) in Europe, and VYVANSE(TM) (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.   

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