PHILADELPHIA, PA and BASINGSTOKE, England, Nov. 6 /CNW/ - 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).
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
"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
"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
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
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
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
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
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:
"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.
(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
(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:
(12). Block GA. (2000) Prevalence and clinical consequences of elevated
Ca x P product in haemodialysis patients. Clin Nephrol; 54(4): 318-24.
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