Philadelphia, Pa. (October 18, 2006) -- ¾ Newly published data from a large, two-year trial published in the November issue of Kidney International report on the effects of chronic kidney disease (CKD) on cognitive function in CKD Stage 5 patients with hyperphosphatemia (high serum phosphorus levels in the blood), who have been treated with phosphate binder therapy.
This study is particularly relevant, as there is evidence that individuals with reduced renal function experience a significantly greater decline in cognitive function compared to those with normal renal function. Such patients also suffer from hyperphosphatemia, a condition that if uncontrolled contributes to the development of secondary hyperparathyroidism, renal osteodystrophy and vascular calcification.
"While CKD Stage 5 patients experience deterioration in their cognitive function, our study documented that this decline is independent of the phosphate-binder therapy used to control their hyperphosphatemia," said lead investigator Paul Altmann, MD, FRCP, consultant nephrologist, Oxford Radcliffe Hospitals in England. "Specifically, the study found that the use of FOSRENOL as a phosphate binder does not negatively affect cognitive function as compared to standard phosphate binder therapy."
In the current analysis, five assessments of participants' attention and memory revealed that deterioration in cognitive function was similar in patients enrolled in a two-year, multicenter study comparing FOSRENOL and standard phosphate binder therapy. Cognitive function declined for most tests in both treatment groups during the study. Notably, the impairments in cognitive function generally related to the speed of task completion, not to the accuracy of test completion.
"Cognitive function is a critical issue for CKD Stage 5 patients, yet there is limited long-term data available in this specific area of study. Shire welcomes the publication of these data, which add further insights into the complex impact of CKD on overall health," said Dr. Raymond Pratt, Vice President, Scientific Leader, Renal Business Unit, Research and Development, Shire Pharmaceuticals.
Study Design Investigators conducted the cognitive function assessments at 41 U.S. sites in a subgroup of hemodialysis patients from a two-year, randomized, open-label comparator study of FOSRENOL versus standard therapy (sevelamer HCl, calcium and aluminum). After a one- to three-week washout period of previous phosphate binders, the patients entered a six-week dose titration period and then a long-term maintenance phase of up to two years' total study participation. Patients started FOSRENOL treatment at 750 milligrams per day (mg/day) or 1,500 mg/day, at the discretion of the investigator. The dose could be titrated up to 3,000 mg/day or down to 375 mg/day, as necessary.
Investigators assessed the participants' cognitive function using computer-controlled tasks from the Cognitive Drug Research (CDR) cognitive assessment system. The first three tasks of the CDR assessed the patient's attention span; the last two tasks were tests of the patient's memory. Researchers conducted the testing before dialysis at the second or third dialysis session of the week at the study start and during visits at 3.5 months (Visit 9), 6 months (Visit 12), 12 months (Visit 15), 18 months (Visit 18) and 24 months (Final Visit).
In total, 124 hemodialysis patients (47 on FOSRENOL; 77 on standard therapy) completed the full two years of treatment and all six cognitive function testing sessions. This study demonstrates that while cognitive function deteriorates in hemodialysis patients over a two-year period, use of FOSRENOL as a phosphate binder does not adversely affect cognitive function as compared with the use of standard therapy.
Managing Hyperphosphatemia Of the approximately 20 million Americans who have some form of kidney disease, more than 530,000 have developed CKD Stage 5. Even with dialysis and a low-phosphorus diet, most CKD Stage 5 patients in the United States will develop hyperphosphatemia (high phosphorus levels in the blood). Without effective treatment, hyperphosphatemia may lead to renal osteodystrophy, a collection of bone diseases characterized by bone pain, brittle bones, skeletal deformities and fractures. Evidence also shows that hyperphosphatemia may contribute to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients. FOSRENOL is not indicated for the treatment of secondary hyperparathyroidism, vascular and nonvascular calcification, or cardiovascular or renal disease.
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 increased by six percent. There are no controlled clinical trials with FOSRENOL demonstrating a reduction in morbidity or mortality.
Hyperphosphatemia is managed with a combination of dialysis, diet restriction and phosphorus-binding agents, since 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.
Despite the availability of phosphorus-binding agents, it remains a challenge for some CKD Stage 5 patients to maintain target ranges. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease, Guideline 3, Evaluation of Serum Phosphorus Levels, fewer than 30 percent of dialysis patients are able to maintain serum phosphorus levels in the target range.
For further information, please contact:
Christine Gerstle – Porter Novelli
212-601-8144
FOSRENOL
FOSRENOL is indicated to reduce serum phosphate in patients with end stage renal disease (ESRD).
FOSRENOL (lanthanum carbonate) 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-only 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, including the reformulated strengths of 500 milligrams (mg), 750 mg and 1.0 gram (g), as well as the original 250 mg. With the reformulated doses, patients can achieve serum phosphorus target levels with as few as three tablets per day. (Dosing based on as few as three tablets per day. Number of meals per day may vary. To achieve certain doses, additional tablets may be required.)
FOSRENOL 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.
FOSRENOL has been clinically tested in more than 5,500 patients. Nearly 1,000 of these patients have been treated with lanthanum carbonate for more than one year. Over 53,000 patients have been treated with FOSRENOL. The long-term safety profile of FOSRENOL shows no evidence of toxicity at clinical doses. Trials involving patients treated with FOSRENOL showed sustained mean serum phosphorus reduction in a majority of patients.
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 pharmaceutical 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 believes that a carefully selected portfolio of products with a strategically aligned and relatively small-scale sales force will deliver strong results.
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Journal
Kidney International