Shire Announces Results of FOSRENOL(R) Study in Pre-Dialysis CKD Stage 3 & 4 Patients (1)

PHILADELPHIA and BASINGSTOKE, England, November 6 /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

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