UK Launch Expands Global Reach of FOSRENOL(R)

UK Launch Expands Global Reach of FOSRENOL(R)

March 06, 2007

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 6 /Xinhua-PRNewswire/ --
Shire plc (LSE: SHP; Nasdaq: SHPGY; TSX: SHQ).  Shire
recently announced the launch of FOSRENOL (lanthanum
carbonate) in the United Kingdom (UK) following the
product's successful approval for the control of
hyperphosphataemia in patients with chronic kidney disease
(CKD) on haemodialysis or continuous ambulatory peritoneal
dialysis (CAPD). 

    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) (lanthanum carbonate)

    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) (>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 .

    "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(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.

    i    Block GA et al. Association of serum phosphorus
and calcium x 
         phosphate product with mortality risk in chronic
hemodialysis 
         patients: A national study. Am J Kidney Dis 1998;
31: 607-617

    ii   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 

    iii  Norris KC. Toward a new treatment paradigm for
hyperphosphataemia in 
         chronic renal disease. Dial Transplant 1998; 27
(12): 767-773	

    iv   Block G, Port FK. 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

    v    Foley R et al. Clinical epidemiology of
cardiovascular disease in 
         chronic renal disease. Am J Kidney Dis 1998; 32
(5) Suppl 3:112-119

    vi   Shire Data on File 08.2644

    vii  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


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