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Shire Pharmaceuticals Group Plc

Shire Announces Results of FOSRENOL(R) Study in Pre-Dialysis CKD Stage 3 & 4 Patients

Philadelphia and Basingstoke, England, November 6 (ots/PRNewswire)
- Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) today announced the
results of a Phase II study indicating that FOSRENOL can effectively
reduce serum phosphate levels in chronic kidney disease (CKD)
patients not on dialysis.(1) FOSRENOL is a non-calcium phosphate
binder, indicated to treat hyperphosphatemia in end stage renal
disease (ESRD), also known as CKD Stage 5.(2)
While the results of this exploratory study did not achieve its
specified primary endpoint (control of serum phosphate to within
normal levels), more FOSRENOL treated patients achieved this goal
than did patients in the placebo arm of this multi-center,
double-blind, placebo-controlled study of 90 pre-dialysis patients
with CKD Stage 3 and 4 and hyperphosphatemia(1) (serum phosphate
above the upper limit of normal, which the body cannot excrete). (3),
(1)
As a secondary endpoint, patients taking FOSRENOL were found to
have statistically significant reductions in serum phosphate levels
after eight weeks of treatment vs those patients in the placebo arm.
The findings complement the conclusions of a recent Shire
initiated U.S. Food and Drug Administration (FDA) Cardiovascular and
Renal Drugs Advisory Committee,(4) which voted by majority to
recommend in favor of phosphate binders extending their label to
treat CKD Stage 4 patients with hyperphosphatemia.
"This study provides valuable insights into the evolution of
kidney disease and the development of the hyperphosphatemic state in
patients with CKD," said Raymond Pratt, vice president and scientific
leader for the Renal Business Unit of Shire Pharmaceuticals. "There
is a paucity of data in this population and this study marks an
important step toward learning more about the management of this
patient population - and importantly, shows that a little bit of
kidney function still goes a long way to maintain phosphate balance."
"The need for effective phosphate management before patients reach
dialysis is recommended by the KDOQI guidelines and is a growing area
of interest and debate. As a company, Shire is committed to continued
research in this area and to understand how effective treatment may
help patients cope with some of the serious complications of kidney
disease."
This Phase II study involved the initial screening of 281 CKD
Stage 3 & 4 patients with 90 randomized to receive either FOSRENOL or
placebo.(1) When investigators looked at the change in phosphate
levels from baseline, they found statistically significant reductions
in serum phosphate at week 8 versus placebo.(5) Serum parathyroid
hormone (PTH) levels were significantly decreased in the
FOSRENOL-treated subjects compared with an increase in the placebo
group. The full results will be submitted for publication and
presentation at upcoming scientific meetings.
Shire is working closely with the FDA to explore the regulatory
pathway forward for phosphate binding medicines in pre-dialysis
patients with CKD Stage 4.
As kidney disease progresses, the kidneys lose the ability to
effectively excrete phosphate and patients ultimately develop
hyperphosphatemia.(6) While the condition is more common when
patients have reached CKD Stage 5, the problem of elevated serum
phosphate can start before patients require dialysis.(6) Phosphate
control is critical for these patients because, if not managed
successfully, hyperphosphatemia 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.(6), (7)
Over 5,200 patients have been treated with FOSRENOL during an
extensive clinical development program,(5) with some having been
followed up for up to six years.(8) In the United States, over 87,000
patients have been prescribed FOSRENOL since it was launched in
2005.(5), (9) 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 phosphate reduction in a majority of patients, with some
patients being followed up over a six-year duration.(8)
FOSRENOL is now available in 23 countries worldwide and has been
met with solid support from the clinical nephrology community,
because it provides a simplified and effective monotherapy treatment
option(2) for the 1.5 million people on dialysis(7) globally who are
at risk from the serious consequences of hyperphosphatemia.
Managing Hyperphosphatemia
Phosphorus, an element found in nearly all foods, is absorbed from
the gastrointestinal tract into the bloodstream.(3) When the kidneys
fail, they no longer effectively remove phosphorus.(3) While the
normal adult range for phosphorus is 2.5 to 4.5 mg/dL,(10) the blood
phosphorus levels of many patients on dialysis often exceed 6.5
mg/dL.(11) Such levels have been linked to a significantly higher
morbidity and mortality risk for patients who have undergone at least
one year of dialysis.(12) Research has shown that for each mg/dL
increase in mean serum phosphorus, the relative risk of death
increases by six percent.(11)
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.(10) 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.(10), (11)
FOSRENOL
FOSRENOL is indicated to reduce serum phosphate in patients with
ESRD.(2)
FOSRENOL is an effective, non-calcium, phosphate binder that
reduces high phosphorus levels in ESRD patients.(2) FOSRENOL is
formulated as an easy-to-use, unflavored, chewable tablet that can be
taken without water,(2) 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.(2) 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.(2) Once bound, the
FOSRENOL/phosphorus complex cannot pass into the bloodstream and is
eliminated from the body, thereby decreasing mean serum phosphorus
levels.
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 US Prescribing Information on FOSRENOL, please visit
http://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: 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
including, but not limited to, the successful development of JUVISTA
(Human TGF beta 3) and GA-GCB (velaglucerase alfa); manufacturing and
commercialization including, but not limited to, the launch and
establishment in the market of VYVANSE(TM)(lisdexamfetamine
dimesylate) (Attention Deficit and Hyperactivity Disorder ("ADHD"));
the impact of competitive products including, but not limited to, the
impact of those on Shire's 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 INTUNIV(TM) (guanfacine extended
release) (ADHD); Shire's ability to secure new products for
commercialization and/or development; 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.
References:
(1). SM Sprague, WF Finn, and P Qiu (2007) Hyperphosphatemia in
Chronic Kidney Disease Stages 3 and 4: Findings from a Randomized,
Multi-Center Trial. Abstract for ASN Renal Week 2007, Filename:
555494
(2). FOSRENOL(R) U.S. PI.
(3). Venes D and CL Thomas, eds. (2001) Cyclopedic Medical
Dictionary. 20th ed. Philadelphia, Pa: FA Davis Company. 1037, 1173,
1543.
(4). U.S. Food and Drug Administration (FDA) Cardiovascular and
Renal Drugs Advisory Committee. Federal Register / Vol. 72, No. 176 /
Wednesday, September 12, 2007 / Notices.
(5). Data on file, Shire U.S., Inc.
(6). National Kidney Foundation. K/DOQI clinical practice
guidelines for bone metabolism and disease in chronic kidney disease.
Am J Kidney Disease 2004; 42: 24-45, 55-63, 69-71.
(7). Vanholder R, et al. (2005) Chronic kidney disease as cause of
cardiovascular morbidity and mortality. Dial Transplant; 20:
1048-1056.
(8). Hutchison AJ and R Pratt. (2005) Evidence for the long-term
safety and tolerability of lanthanum carbonate. Poster presented at
38th annual meeting of the American Society of Nephrology,
Philadelphia, PA. November 8-13.
(9). Verispan's Total Patient Tracker: January 2005-August 2007.
(10). Moe SM. Calcium, phosphorus and vitamin d metabolism in
renal disease and chronic renal failure. In: Kopple JD and SG Massry,
eds. Nutritional Management of Renal Disease. Philadelphia, PA:
Lippincott Williams & Wilkins; 2004: 261.
(11). Block GA, Hulbert-Shearon TE, Levin NW and FK Port. (1998)
Association of serum phosphorus and calcium x phosphate product with
mortality risk in chronic hemodialysis patients: A national study. Am
J Kidney Dis; 31: 607-617.
(12). Block GA. (2000) Prevalence and clinical consequences of
elevated Ca x P product in haemodialysis patients. Clin Nephrol;
54(4): 318-24.

Contact:

Ann Blumenstock, Resolute (ex-US.), Phone: +44-207-357-8187, Cell:
+44-7788-543-537, Email: Ann.blumenstock@resolutecommunications.com;
Carrie Fernandez, Porter Novelli (US), Phone: +1-212-601-8336, Cell:
+1-917-202-5553, Email: carrie.fernandez@porternovelli.com.

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