PHILADELPHIA, Oct. 24 /PRNewswire/ -- A newly published study in Nephron Clinical Practice this month shows FOSRENOL(R) (lanthanum carbonate) successfully reduces and maintains mean serum phosphate levels for up to three years, while demonstrating safety and tolerability in patients with end-stage renal disease (ESRD).
This study is promising news for the nearly one million people worldwide who are at risk from the serious consequences of hyperphosphatemia, which has been shown to be associated with long-term morbidity and mortality. As a condition in which there is an excess amount of phosphate in the blood, hyperphosphatemia is an almost inevitable consequence of ESRD, and remains poorly controlled in a significant proportion of patients.
Dr. Alastair Hutchison, the trial’s lead investigator from the Manchester Institute of Nephrology & Transplantation, Manchester, UK said, “These data are very compelling and demonstrate the safety, tolerability and effectiveness of FOSRENOL(R) at reducing phosphate levels in patients long-term. FOSRENOL(R) is also associated with a lower tablet burden, an important benefit for renal disease patients who are often already taking multiple medications. The results add to the already extensive data package available for FOSRENOL(R) and further support this effective treatment as a significant step forward in phosphate management.”
The results are from study extensions initially involving 518 and 161 patients treated with FOSRENOL(R) for periods of up to 1 and 3 years, respectively.* Prior to the extensions, those patients taking FOSRENOL(R) were continued on the treatment, and those receiving calcium carbonate were switched to FOSRENOL(R). At the end of the first, six-month study extension, the mean serum phosphate level in those patients continuing on FOSRENOL(R) was 5.5 mg/dl (1.78 mmol/L). By the end of the second, two-year extension, serum phosphate levels were less than or equal to 5.6 mg/dl (1.8 mmol/L) in 69% of patients receiving FOSRENOL(R) in all phases of the trial, demonstrating the long-term efficacy of FOSRENOL(R) at reducing the incidence of hyperphosphatemia. At the time the study was conducted, the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines target for serum phosphate was 5.6 mg/dl (1.8 mmol/L). Furthermore, prior to the extension, following discontinuation of calcium carbonate and switching to FOSRENOL(R), the incidence of hypercalcemia dropped to 2.7% compared to 20.2% during the double-blind phase. During this trial FOSRENOL(R) was also shown to be well tolerated over the long-term.**
Dr. Ray Pratt, Vice President Shire Global Clinical Medicine, commented, “Shire is very pleased at the publication of these data. They further demonstrate the robust evidence supporting the safety, effectiveness and tolerability of FOSRENOL(R) in dialysis patients with hyperphosphatemia. FOSRENOL(R) is currently available in the US and will be launched across Europe over the coming months. Shire is very proud to be able to provide a successful calcium-free alternative to patients in need of an effective and well-tolerated phosphate binder.”
Hyperphosphatemia is a relatively unrecognized medical condition even though it affects as many as 224,000 people in the United States and 180,000 in Europe. Unfortunately, the condition is almost an inevitable consequence of chronic renal failure due to the body’s reduced ability to rid itself of excess phosphate, which enters the body during daily dietary intake.
If not managed successfully, hyperphosphatemia may cause serious long-term health risks leading to renal osteodystrophy (resulting in bone pain, brittle bones and skeletal deformities), and potentially contributing to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients.
Dialysis patients are on a challenging and unpalatable low phosphate diet to help with this issue, and although dialysis itself attempts to address this imbalance, studies show many patients receiving dialysis have serum phosphate levels exceeding 6.5 mg/dl (2.1 mmol/L), far beyond the current K/DOQI guidelines upper limit of 5.5 mg/dl (1.78 mmol/L). Phosphate binder therapy is therefore critically important to achieve phosphate control.
Despite the availability of several phosphate binders, current phosphate management remains problematic. Data from over 6,000 hemodialysis patients revealed a mean serum phosphate level of 6.2 mg/dL (2.0 mmol/L) and as many as 30% of patients even had levels above 7.0 mg/dL (2.26 mmol/L). These new data demonstrate that FOSRENOL(R) has the potential to improve the management of hyperphosphatemia.
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(R) compared to alternative therapy for up to three years. The duration of treatment exposure and time of observation in the clinical program are too short to conclude that FOSRENOL(R) 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(R) clinical studies. Caution should be used in patients with these conditions. FOSRENOL(R) should not be taken by patients who are nursing or pregnant. FOSRENOL(R) should not be taken by patients who are under 18 years of age.
Managing Hyperphosphatemia
Phosphorus, an element found in nearly all foods, is absorbed from the gastrointestinal tract into the blood stream. When the kidneys fail, they no longer effectively filter out phosphates, even with the help of blood- cleansing dialysis machines. While the normal adult range for phosphorus is 2.5 to 4.5 mg/dL, the blood phosphorus levels of the majority (60%) of patients on dialysis exceed 5.5 mg/dL. Such levels have been linked to a significantly higher illness and death risk for patients who have undergone at least one year of dialysis.
Hyperphosphatemia disrupts the delicate interplay between the body’s levels of calcium, parathyroid hormone (PTH) and vitamin D. Over time, hyperphosphatemia can ultimately lead to calcification of the heart, lung and some arteries. Evidence shows that hyperphosphatemia contributes to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients. In fact, studies have shown that cardiovascular mortality in dialysis patients aged 25-34 years is more than five times greater than that in people aged 65-74 in the general population.
Since diet restrictions alone generally cannot control phosphate levels, patients traditionally manage hyperphosphatemia with phosphate binding agents. Such binders “soak up” phosphate in the gastrointestinal tract, before it can be absorbed into the blood. These agents can be associated with patient management issues including potential side effects such as hypercalcemia and tolerability problems. Patient compliance with phosphate binding agents can also be challenging due to the many medications ESRD patients must take.
FOSRENOL(R)
FOSRENOL(R), which received FDA approval in October 2004, is formulated as an easy-to-use, chewable only tablet that can be taken without water, an important advantage for ESRD patients who must restrict their fluid intake. FOSRENOL(R) launched in January 2005 and is available in 250 mg and 500 mg strengths. The recommended initial daily dose of FOSRENOL(R) is 750 to 1,500 mg for adults; physicians should adjust the dose to reach target serum phosphorus levels. Most patients require a total daily dose between 1,500 mg and 3,000 mg to achieve serum phosphorus control, which equates to one to two FOSRENOL(R) tablets per meal. The daily dose should be divided and taken with, or immediately after, meals.
Notes to Editors:
Study Details
* Patients who participated in a six-month, randomized trial comparing lanthanum carbonate with calcium carbonate were eligible for the study extensions. The first part was a six-month extension carried out at 67 centers in the UK, Germany, Belgium and The Netherlands involving 518 patients. 161 of these patients were then entered into the second part, which was a two-year extension carried out at 34 of these centers in the UK, Germany and Belgium. FOSRENOL(R)-treated patients from the initial randomized trial continued taking the drug in the extensions and calcium carbonate-treated patients were switched to FOSRENOL(R), 375-3000 mg/day, prior to the extensions.
**During the trial, few adverse events were considered to be drug-related (2.8%) and, given that the majority were classified as mild-to-moderate in severity, few adverse events led to patient withdrawal from the studies (2.4%). 46 patients were able to continue receiving lanthanum carbonate with no increase in the annual incidence of adverse events indicating a favorable safety profile for lanthanum carbonate treatment.
Shire
Shire is a global specialty pharmaceutical company with a strategic focus on meeting the needs of the specialist physician and currently focuses on developing and marketing products in the areas of central nervous system (CNS), gastrointestinal (GI), renal diseases and human genetic therapies. Shire has operations in the world’s key pharmaceutical markets (US, Canada, UK, France, Italy, Spain and Germany) as well as a specialist drug delivery unit in the US.
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