Shire Announces Launch of FOSRENOL(R) in Japan

    DUBLIN, March 11 /CNW/ - Availability of Non-Calcium, Non-Resin
FOSRENOL(R) Gives New Therapy Choice for the Management of Hyperphosphataemia
in End-Stage Renal Disease Patients(1) in Japan
    Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty
biopharmaceutical company, today announces the Japanese launch of FOSRENOL(R)
(lanthanum carbonate), which is now available to prescribers and patients in
Japan through Shire's strategic alliance partner Bayer Yakuhin Ltd.
    FOSRENOL is the first commercially available non-calcium, non-resin
phosphate binder in Japan and is used in the control of hyperphosphataemia in
chronic renal failure patients on dialysis.
    Bayer Yakuhin received an exclusive license from Shire in December 2003
to develop FOSRENOL in Japan, completing Phase II and Phase III clinical
trials in the Japanese population.
    Studies based on widespread screening programs in Japan indicate the
country has an extremely high prevalence of chronic kidney disease (CKD), with
an estimated 20 per cent of the total adult population of 103.2 million living
with some form of the condition(2). The number of dialysis patients in Japan
is estimated at approximately 270,000(3), and is increasing by 10,000 per
year(4).
    A direct consequence of declining kidney function is the inability to
adequately control serum phosphate levels, which leads to hyperphosphataemia5.
Elevated phosphate causes disruption in the delicate interplay between the
body's levels of calcium, parathyroid hormone and vitamin D. This can lead to
bone disorders, impaired bone reservoir function (the bone acts as an
important reservoir for phosphate and calcium) and, ultimately, vascular
calcification(5). This triad of interrelated abnormalities is known as chronic
kidney disease-mineral and bone disorder(6).
    Improving bone reservoir function through sustained phosphate control is
an important component in preventing vascular calcification(7). Vascular
calcification scores help predict mortality in CKD patients(8) and
improvements in bone turnover are associated with lower progression of
calcification scores(9). Currently, the most commonly prescribed phosphate
binder in Japan is calcium carbonate. However, calcium-based phosphate binders
have been linked with increased calcium load(10) and the progression of
vascular calcification(7).
    FOSRENOL delivers sustained phosphate control(11) and over two years in
CKD5D patients has been shown to improve bone turnover and volume(12).
FOSRENOL is generally well-tolerated, with a predictable tolerability profile
observed during the course of treatment for up to six years(11).
    "There is a clear medical need in Japan for an effective phosphate binder
that provides sustained phosphate control and does not directly contribute to
calcium load," said Shirley Wakelin, General Manager FOSRENOL, Shire.
    "Shire is proud of its ongoing commitment to renal medicine as it makes
FOSRENOL available to an increasing number of patients around the world.
Launch in Japan is a key step forward for the brand and represents an
important new therapy choice for patients living with ESRD. We are delighted
to enter into this new phase of partnership with Bayer, a strongly-established
healthcare company with expertise across multiple specialty therapy areas."
    With the launch in Japan, FOSRENOL is now available in 33 markets
worldwide and further launches are planned throughout 2009.

    Notes to Editors

    About Phosphate

    Phosphate, which is found in nearly all foods, is absorbed from the
gastrointestinal (GI) tract into the blood stream. When the kidneys fail, they
do not effectively remove sufficient phosphate, even with the help of
blood-cleansing dialysis. While the normal adult range for phosphate is
0.8mmol/L (2.5 mg/dL) to 1.4mmol/L (4.5 mg/dL), the blood phosphate levels of
many patients on dialysis can exceed 2.1mmol/L (6.5 mg/dL)(13). Such levels
have been linked to a significantly higher complications and risk of death for
patients who have undergone at least one year of dialysis14 with over 70 per
cent of these patients developing hyperphosphataemia(15).
    CKD disrupts the delicate interplay between the body's levels of calcium,
parathyroid hormone and vitamin D, leading to hyperphosphataemia and chronic
kidney disease-mineral and bone disorder(16). Over time, hyperphosphataemia
can ultimately lead to calcification in the heart, lung and some arteries(17).
Accumulating evidence shows that hyperphosphataemia contributes to
cardiovascular disease(18), which accounts for almost half of all deaths among
dialysis patients(19). Studies have shown that cardiovascular mortality in
dialysis patients aged 25-34 years is more than five times greater than that
in people aged 65-74 in the general population(20).
    Since dialysis and diet restrictions alone generally cannot control
phosphate levels, patients need to manage hyperphosphataemia by taking
phosphate binding agents with food. Such binders "soak up" phosphate in the
gastrointestinal tract, before it can be absorbed into the blood.

    About FOSRENOL(R) (lanthanum carbonate)

    FOSRENOL is indicated as a phosphate binding agent for use in the control
of hyperphosphataemia in chronic renal failure patients on haemodialysis or
continuous ambulatory peritoneal dialysis(1).
    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(1). As a
consequence, overall phosphate absorption from the diet is decreased
significantly.
    FOSRENOL is available in a broad range of dosage strengths including
500mg, 750mg, and 1000mg tablets(1). Patients taking FOSRENOL can achieve
sustained phosphate control with as little as one tablet per meal.
    FOSRENOL was first approved in Sweden, in March 2004 and by the US FDA in
October 2004. FOSRENOL was subsequently approved in all EU markets by the
European Mutual Recognition Procedure and is now launched in 33 markets
worldwide. It continues to be approved and made available in new markets
around the world.

    Important Safety Information

    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 are gastrointestinal
reactions such as abdominal pain, constipation, diarrhoea, dyspepsia,
flatulence, nausea and vomiting. These are minimized by taking FOSRENOL with
food and generally abate with time with continued dosing. Hypocalcaemia was
the only other commonly reported adverse reaction. Full prescribing
information is available on request.

    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 hyperactivity
disorder, human genetic therapies and gastrointestinal diseases as well as
opportunities in other therapeutic areas to the extent they arise through
acquisitions. Shire's in-licensing, merger and acquisition efforts are focused
on products in specialist markets with strong intellectual property protection
and global rights. Shire believes that a carefully selected and balanced
portfolio of products with strategically aligned and relatively small-scale
sales forces will deliver strong results.
    For further information on Shire, please visit the Company's website:
http://www.shire.com.
    Shire is proud to be an official partner of World Kidney Day (WKD),
Thursday 12 March 2009. For further information on WKD visit
http://www.worldkidneyday.org

    About Bayer Yakuhin Ltd

    Bayer Yakuhin Ltd., headquartered in Osaka, is a healthcare company which
combines business activities of Bayer Schering Pharma (pharmaceuticals),
Consumer Care (OTC product), Diabetes Care (Diabetes care product), and Animal
Health (companion and food animal products). Bayer Schering Pharma Division is
focused on the following areas: Diagnostic Imaging, Primary Care, Oncology,
Speciality care and Women's Healthcare. With innovative products, Bayer
Yakuhin aims for leading positions in specialized markets in Japan. Using new
ideas, Bayer Yakuhin aims to make a contribution to medical progress and
strives to improve the quality of life.
    For further information on Bayer Yakuhin Ltd please visit the Company's
website: http://www.bayer.co.jp/byl

    References

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    3.  Yusuke Tsukamoto. End-Stage Renal Disease and its Treatment in Japan;
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