Shire Pharmaceuticals Group's Fosrenol Does Not Meet Main Goal of Trial
PHILADELPHIA and BASINGSTOKE, England, November 6 -- Shire plc 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.
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 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'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.