Shire Demonstrates Commitment to Improving Patient Adherence in End Stage Renal Disease as New Phosphate-Binder FOSRENOL(R) Launches in Europe

Shire Demonstrates Commitment to Improving Patient Adherence in End Stage Renal Disease as New Phosphate-Binder FOSRENOL(R) Launches in Europe

June 25, 2007

     -- New Research Provides Important Insights Into
Adherence Issue

     -- Data Reveal Perceptual and Practical Barriers
Including the Need for 
        Phosphate Binders With Simplified Dosing

    BASINGSTOKE, England, June 25 /Xinhua-PRNewswire/ --
Shire plc (LSE: SHP; Nasdaq: SHPGY; TSX: SHQ). New data
from a patient adherence survey presented on Friday 22nd
June at the XLIV ERA-EDTA Congress in Barcelona highlight
that over 40% of patients with chronic kidney disease (CKD)
forget to take their phosphate-binding medication.(1)
Phosphate binders are used to treat hyperphosphataemia
(unusually high levels of phosphorous in the blood), which,
if not managed successfully, can lead to serious health
consequences including increased rates of cardiovascular
morbidity and mortality and other complications.(2)

    The research reveals that poor patient adherence to
phosphate binders is linked to practical barriers such as
the complexity of the dosing regimen and not understanding
how to take them, as well as perceptual barriers regarding
patient beliefs about their need for medication and
concerns about adverse events.(1)

    Rob Horne, Professor of Behavioural Medicine at the
School of Pharmacy, University of London, conducted the
research which assessed the behavioural patterns of 221
patients with CKD across 8 centres in the UK.

    "CKD can have a devastating impact on patients'
lives. The study shows that adherence to phosphate-binding
medication is adversely affected by a number of factors,
both practical and perceptual," said Professor Horne.
"On the practical side, daily treatment requires often
complex dosing schedules on top of an already difficult
treatment regimen. This can include long dialysis sessions,
strict fluid and dietary restrictions and a complicated
medication schedule involving up to 25 tablets per day.
Phosphate binders used to manage hyperphosphataemia can
alone add up to 12 tablets per day."

    "On the perceptual side, it is essential to
recognise that personal beliefs about the value of
medication are important. Our study showed that non
adherence was linked to doubts about the need for treatment
and concerns about taking phosphate binders. We now need to
develop more effective methods for helping patients to get
the best from their medicines by facilitating informed
choice and improved adherence. This should involve the
provision of bespoke information to meet individual needs
and address concerns as well as efforts to overcome the
practical barriers to adherence by making the regimen as
convenient and easy to use as possible," he added.

    The research, using validated questionnaires(1),
produced the following findings:

    -- Over 40% of patients forgot to take their
phosphate-binder medication 
       sometimes, often or always;

    -- 38% forgot to take their medication at mealtimes;

    -- 23% of patients reported altering their dose;

    -- 19% decided to miss doses;

    -- 21% took less medication than instructed.(1)

    Over 70%(3) of the estimated 1.5 million people with
CKD on dialysis worldwide(4) will develop
hyperphosphataemia due to their failing kidneys being
unable to effectively rid their bodies of the excess
phosphate absorbed from food. If not managed successfully,
hyperphosphataemia can lead to serious health problems
including renal osteodystrophy (a bone disorder resulting
in painful, brittle bones that may fracture or lead to
deformities) and cardiovascular disease which accounts for
almost half of all deaths in dialysis patients.(5)

    Despite the availability of existing therapies,
effective phosphate management remains a challenge with up
to 75% of dialysis patients exceeding the National Kidney
Foundation Kidney Disease Outcomes Quality Initiative
(NKF/KDOQI) guidelines for serum phosphate levels less than
1.78 mmol/L (5.5 mg/dL).(6)

    "This research highlights that a combination of
treatment factors, including tablet burden, can contribute
to poor patient adherence which may compromise their
ability to meet specified global targets for phosphate
levels," said Professor Horne.

    FOSRENOL is a newly introduced treatment option in
Europe for the nephrologist to use in the management of
hyperphosphataemia in CKD patients on dialysis. It is a
non-calcium based binder with a high affinity for phosphate
that binds to the phosphate in food to effectively reduce
serum phosphorous levels.(7) FOSRENOL can be used
effectively as a monotherapy and is associated with a lower
tablet burden than existing phosphate binders with the
majority of patients requiring just one chewable tablet
during each meal.(8) This compares to other therapies that
are often used in combination and may require up to 12
tablets per day. This simplified dosing regime may remove
some of the practical barriers to patient adherence
identified in the research.

    "Adherence is emerging as a key issue for patients
with CKD, with many still having phosphate levels above the
recommended global target. Shire is sponsoring Professor
Horne's research as part of its commitment to exploring new
ways to improve patient adherence and ultimately better
patient outcomes," said David Milton, Senior Vice
President, Shire Renal Business Unit. "FOSRENOL is our
effective phosphate binder that offers the added benefit of
a reduced pill burden with the majority of CKD patients on
dialysis requiring just one tablet during each meal. As
part of this commitment, Shire is also developing
additional FOSRENOL formulation options aimed at making it
even simpler for patients," he added.

    Over 5,000 patients have been treated with FOSRENOL
during an extensive clinical development programme(9), with
a small number having been followed up for up to six
years.(10) In the US, over 76,000 patients have been
prescribed FOSRENOL since it was launched in 2005.(11)

    FOSRENOL is now available in 20 countries, including
Canada, France, Germany, Italy, UK and the US and continues
to be launched in new markets around the world.

    References:

    1. Horne R et al. Adherence to phosphate binding
medication: Insights from a survey using validated
questionnaires. Presented at the XLIV ERA-EDTA Congress,
Barcelona, Spain, 21-24 June, 2007.

    2. 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.

    3. Albaaj F, Hutchison AJ. Lanthanum carbonate for the
treatment of hyperphosphataemia in renal failure and
dialysis patients. Expert Opin. Pharmacother 2005; 6(2):
319-328.

    4. Global dialysis. Global dialysis: dialysis standards
and statistics. Available at
http://www.globaldialysis.com/stats.asp . Accessed on 18
May 2007.

    5. The National Institutes of Health National Institute
of Diabetes and Digestive and Kidney Diseases. U.S. Renal
Data System, USRDS 2005 Annual Data Report: Atlas of
End-Stage Renal Disease in the United States. Available at
http://www.usrds.org/2005/pdf/06_morb_and_mort_05.pdf .
Accessed on 18 May 2007.

    6. 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.

    7. Hutchison AJ, Maes B, Vanwalleghem J et al.
Long-term efficacy and tolerability of lanthanum carbonate:
results from a 3-year study. Nephron Clin Pract
2006;102(2):c61-c71.

    8. 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.

    9. Shire Data on File 08.2644.

    10. 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.

    11. Verispan 2007, Verispan Total Patient Tracker.

    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 over 70 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 authorisation for FOSRENOL in sixteen
member states, thus completing the first step in securing
marketing approval throughout Europe. Later, the European
process was completed resulting in recommendation for
approval in the remaining 11 member states. FOSRENOL is now
available in 20 countries, including Canada, France,
Germany, UK and the US and continues to be launched in new
markets 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 minimised 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 biopharmaceutical 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 materialise, 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 commercialisation; 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
date of SPD503 (guanfacine extended release) (ADHD);
Shire's ability to secure new products for
commercialisation and/or development; Shire's ability to
benefit from its acquisition of New River Pharmaceuticals
Inc.; the successful development of JUVISTA and other risks
and uncertainties detailed from time to time in Shire 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, 2006.

    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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