FDA Advisory Committee Votes in Favor of Earlier Use of Phosphate Binders in Stage 4 Kidney Disease Patients With Hyperphosphatemia

Philadelphia (ots/PRNewswire) -

At the U.S. Food and Drug Administration's (FDA's) Cardiovascular
and Renal Drugs Advisory Committee meeting today, the majority of
members voted to recommend the use of phosphate binders, including
Shire Pharmaceuticals' non-calcium FOSRENOL(R) (lanthanum carbonate),
to treat hyperphosphatemia (elevated levels of phosphorus in the
blood) in chronic kidney disease (CKD) Stage 4 patients. Currently,
FOSRENOL is indicated to reduce serum phosphate in patients with end
stage renal disease (ESRD).

The Committee did not reach consensus on which additional studies
may be required, and Shire will work closely with the FDA to agree
upon the pathway forward. The FDA Advisory Committee's recommendation
is not binding on the FDA, and no time has been set by which the FDA
will decide whether to follow this recommendation.

CKD is divided into five stages based on the level of kidney
function, with higher stages of disease representing lower kidney
filtration rates. In the United States, approximately 20 million
adults have some form of CKD, of whom 500,000 have developed ESRD (or
CKD Stage 5). An additional 400,000 individuals have significant loss
of kidney function and are classified as having CKD Stage 4.
Worldwide, almost 1.5 million people with CKD are on dialysis.

"As the Committee heard today, CKD patients are at an increased
risk of death. In fact, a 30-year-old dialysis patient has the same
risk of death as that of a 90-year-old with normal kidney function,"
said Keith Hruska, M.D., Professor of Pediatrics, Medicine and Cell
Biology, Director, Division of Pediatric Nephrology, Washington
University School of Medicine. "These patients that progress to
dialysis represent the 'survivors.' That's why it's important to help
kidney patients stay as healthy as possible from the early stages of
their disease."

As a result of ongoing dialogue with the FDA, Shire had requested
that an Advisory Committee Meeting be convened to provide guidance on
the studies needed to expand the use of phosphate binders. Following
these discussions, the FDA formally invited all three sponsors who
presented at today's meeting to collaborate on demonstrating their
case for treating CKD Stage 4 and 5 patients who have
hyperphosphatemia with phosphate binders.

"Shire is committed to offering its effective phosphate binder,
FOSRENOL, to kidney patients who need protection from the
complications of elevated serum phosphorus," said Joseph Schlitz,
vice president, U.S. Renal Business, Shire Pharmaceuticals. "The high
affinity of FOSRENOL for phosphate provides effective monotherapy in
a simple dosing regimen, which is one tablet per meal for most
patients. Along with its well-established safety profile, FOSRENOL
offers an attractive solution for both patients and their healthcare
providers. Shire is therefore confident that FOSRENOL is well suited
to be a first-line, non-calcium treatment of choice for CKD Stage 4
patients."

While the normal adult range for serum phosphorus is 2.5 to 4.5
milligrams per deciliter (mg/dL), the serum phosphorus levels of many
patients on dialysis often exceed 6.5 mg/dL. The National Kidney
Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI)
guidelines recommend that monitoring for hyperphosphatemia should
begin in patients with CKD Stage 3, and that serum phosphorus should
be maintained within the target range of 2.7 to 4.6 mg/dL in patients
with CKD Stages 3 and 4, or 3.5 to 5.5 mg/dL for CKD Stage 5.

"Based on data in dialysis patients, it is reasonable to expect
that treating pre-dialysis patients for secondary conditions, such as
hyperphosphatemia, may slow the progression of their bone and
cardiovascular disease," said Hartmut H. Malluche, M.D., chief,
Nephrology, Bone and Mineral Metabolism, Department of Internal
Medicine, University of Kentucky College of Medicine. "Studies have
shown that FOSRENOL also is associated with a trend toward positive
bone health -- a treatment attribute that also may be of benefit to
CKD Stage 4 patients."

Most CKD Stage 4 and 5 patients will develop chronic kidney
disease-mineral and bone disorder (CKD-MBD) -- a systemic disorder of
mineral and bone metabolism due to CKD. CKD-MBD often manifests as
hyperphosphatemia, which causes bone disease characterized by bone
pain, brittle bones, skeletal deformities and fractures, and vascular
or other soft tissue calcification. Evidence also shows that
hyperphosphatemia contributes to cardiovascular disease, which
accounts for almost half of all deaths among dialysis patients.

"Shire recently completed a multicenter, placebo-controlled study
in patients with CKD Stages 3 and 4 with hyperphosphatemia. The
results showed that FOSRENOL-treated patients had statistically
significant reductions in serum phosphate levels compared to placebo
after eight weeks of treatment. This study provided valuable insights
into controlling hyperphosphatemia in CKD Stages 3 and 4 patients,"
said Ray Pratt, M.D., vice president, scientific leader, Renal
Business Unit, Research and Development, Shire Pharmaceuticals. "We
are committed to offering all patients the most effective phosphate
binder therapy and will continue to invest in a clinical program that
includes the development of additional FOSRENOL formulation options
aimed at further simplifying treatment for all CKD patients."

Managing Hyperphosphatemia

Phosphorus, an element found in nearly all foods, is absorbed from
the gastrointestinal tract into the bloodstream. When the kidneys
fail, they no longer effectively remove phosphorus. While the normal
adult range for phosphorus is 2.5 to 4.5 mg/dL, the blood phosphorus
levels of many patients on dialysis often exceed 6.5 mg/dL. Such
levels have been linked to a significantly higher morbidity and
mortality risk for patients who have undergone at least one year of
dialysis. Research has shown that for each mg/dL increase in mean
serum phosphorus, the relative risk of death increases by six
percent.

Hyperphosphatemia is managed with a combination of dialysis, diet
restriction, and phosphorus-binding agents, because diet and dialysis
alone generally cannot adequately control phosphorus levels. Such
binders "soak up" phosphorus in the gastrointestinal tract, before it
can be absorbed into the blood, and aid patients in maintaining
acceptable levels of mean serum phosphorus.

FOSRENOL

FOSRENOL is indicated to reduce serum phosphate in patients with
ESRD.

FOSRENOL is an effective, non-calcium, phosphate binder that
reduces high phosphorus levels in ESRD patients. FOSRENOL is
formulated as an easy-to-use, unflavored, chewable tablet that can be
taken without water, an important consideration for ESRD patients who
must restrict their fluid intake.

FOSRENOL is available in a broad range of dosage strengths
comprised of 500-milligram (mg), 750-mg, and 1-g tablets. Patients
taking FOSRENOL can achieve serum phosphorus target levels with as
few as three tablets per day. (Dosing based on three meals per day.
Number of meals per day may vary. To achieve certain doses,
additional tablets may be required.)

FOSRENOL has a high affinity for phosphate and works by binding to
dietary phosphorus in the gastrointestinal tract. Once bound, the
FOSRENOL/phosphorus complex cannot pass into the bloodstream and is
eliminated from the body, thereby decreasing mean serum phosphorus
levels.

To date, FOSRENOL has been clinically tested in more than 5,200
patients globally, with nearly 1,000 of these patients having been
followed for more than one year. In addition, more than 87,000
patients have been prescribed FOSRENOL in the U.S. alone. FOSRENOL
has the most extensive long-term safety data package of any phosphate
binder and is generally well tolerated. Trials involving patients
treated with FOSRENOL showed sustained serum phosphorus reduction in
a majority of patients, with some patients being followed over a
six-year duration.

FOSRENOL is now available in 23 countries, including Canada,
France, Germany, Italy, and the UK, and continues to be launched in
new markets around the world.

Important Safety Information

The most common adverse events were gastrointestinal, such as
nausea and vomiting, and generally abated over time with continued
dosing. The most common side effects leading to discontinuation in
clinical trials were gastrointestinal events (nausea, vomiting, and
diarrhea). Other side effects reported in trials included dialysis
graft complications, headache, abdominal pain, and hypotension.
Although studies were not designed to detect differences in risk of
fracture and mortality, there were no differences demonstrated in
patients treated with FOSRENOL compared to alternative therapy for up
to three years. The duration of treatment exposure and time of
observation in the clinical program were too short to conclude that
FOSRENOL does not affect the risk of fracture or mortality beyond
three years. While lanthanum has been shown to accumulate in the GI
tract, liver, and bone in animals, the clinical significance in
humans is unknown. Patients with acute peptic ulcer, ulcerative
colitis, Crohn's disease, or bowel obstruction were not included in
FOSRENOL clinical studies. Caution should be used in patients with
these conditions. FOSRENOL should not be taken by patients who are
nursing or pregnant. FOSRENOL should not be taken by patients who are
under 18 years of age.

For Full Prescribing Information on FOSRENOL, please visit
www.fosrenol.com.

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'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. Shire believes that a carefully selected
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: 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
date of SPD503 (guanfacine extended release) (ADHD); Shire's ability
to secure new products for commercialization 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.

Web site: http://www.shire.com
http://www.fosrenol.com

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