Healthcare Industry News: SPD476
News Release - April 21, 2006
FOSRENOL(r) Significantly Reduces Tablet Burden for End-Stage Renal Disease Patients With Hyperphosphatemia and Improves Patient and Physician Satisfaction, a New Study ReportsAdditional Data Reveal That Higher Initial Doses of FOSRENOL(r) Result in More Rapid Control of Mean Serum Phosphorus Than Lower Initial Doses
CHICAGO, Ilinois, April 21 (HSMN NewsFeed) -- According to data presented today at the National Kidney Foundation's (NKF) 2006 clinical meeting in Chicago, IL, a conversion to the non-calcium phosphate binder FOSRENOL(r) (lanthanum carbonate) from other phosphate binder therapies provides continued mean serum phosphorus control for end-stage renal disease (ESRD) patients with hyperphosphatemia, while significantly reducing their daily tablet burden and the total daily dose of phosphate binder medication.
This naturalistic ("real world"), large-scale phase IV, open-label, multicenter trial (n=2,520), was designed to evaluate efficacy, patient and physician satisfaction, and daily dose and tablet burden compared with previous phosphate binder therapy. In addition to reducing tablet burden, changing to FOSRENOL(r) from other therapies resulted in significant improvements in both patient and physician satisfaction with phosphate binder therapy. Both patients and physicians preferred FOSRENOL(r) (lanthanum carbonate) over sevelamer hydrochloride (HCI) and calcium-based phosphate binders in a naturalistic study.
"Successfully managing hyperphosphatemia is a challenge for most ESRD patients due to the exceedingly restrictive diet they must follow and the high tablet burden associated with traditional phosphate binder therapies," said Nirupama Vemuri, MD, South Florida Nephrology Group, Coral Springs, FL. "By significantly reducing phosphate binder tablet burden, FOSRENOL(r) may help improve patient compliance, as well as clinical outcomes for patients with hyperphosphatemia."
At baseline, 52 percent of physicians expressed overall satisfaction with their phosphate binder therapies compared with 84 percent following 12 weeks of treatment with FOSRENOL(r) (p<0.0001). Among patients who completed 12 weeks of treatment (n=1,862), baseline satisfaction was 67 percent, and this increased to 84 percent after 12 weeks of treatment with FOSRENOL(r) (p<0.0001).
This study showed approximately a 30 to 40 percent reduction in tablet burden overall, and up to a 56 percent reduction in tablet burden compared with combination therapy. Since early 2006, a new higher dosage formulation of FOSRENOL(r) has been available. The new formulation, which offers a reduced tablet size, may allow an additional 50 percent reduction over the FOSRENOL® doses used in the study. Patients may be able to take just one tablet per meal. (Dosing based on three meals per day. Number of meals per day may vary. To achieve certain doses, additional tablets may be required.)
Higher Initial Doses of FOSRENOL(r) More Rapidly Control Mean Serum Phosphorus
Additional data being presented at the NKF meeting (an analysis of two previously reported clinical studies) demonstrate that higher initial doses of FOSRENOL(r) can help ESRD patients more rapidly control hyperphosphatemia, without a dose-related increase in adverse events. Patients taking 1,350 mg of FOSRENOL per day achieved phosphorus control after a median treatment duration of 14 days, whereas those taking 2,250 mg/day achieved control in just seven days. (The recommended initial daily dose of FOSRENOL(r) is 750-1,500 mg and the dose should be titrated every two to three weeks until an acceptable serum phosphate level is reached.)
Further, the study found that the doses of FOSRENOL(r) needed to control mean serum phosphorus levels were related to patients' baseline mean serum phosphorus levels, with higher baseline values predicting the need for higher FOSRENOL(r) doses.
"To prevent the serious, long-term complications of hyperphosphatemia, patients must achieve and maintain target mean serum phosphorus levels-a difficult goal for many ESRD patients," said George Porter, MD, FACP, Division of Nephrology and Hypertension, Oregon Health Sciences University. "This study shows that adjusting initial FOSRENOL(r) doses according to pretreatment serum phosphorous levels may help accelerate serum phosphorus control in ESRD patients."
Of the approximately 20 million Americans who have some form of kidney disease, more than 530,000 have developed ESRD. Even with a low-phosphorus diet, most ESRD 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. 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. 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, 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 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 morality.
Hyperphosphatemia is managed with a combination of diet restriction and phosphorus-binding agents, since diet 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 ESRD patients to maintain target ranges. According to the 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.
The K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease also note in Guideline 5, Use of Phosphate Binders in Chronic Kidney Disease (CKD), that non-calcium and non-aluminum phosphate binders are a first-line treatment option in lowering serum phosphorus levels.
FOSRENOL® (lanthanum carbonate) is indicated to reduce serum phosphate in patients with end stage renal disease.
FOSRENOL® 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 advantage for ESRD patients who must restrict their fluid intake. (Tablets are to be chewed completely before swallowing - intact tablets should not be swallowed.)
FOSRENOL® is now available in a broader range of dosage strengths, including the newly formulated higher strengths of 750 milligrams (mg) and 1.0 gram (g), as well as the original 250 mg and 500 mg strengths. With the newly formulated higher strength doses, patients may need to take only one tablet per meal to reach target levels of mean serum phosphorus. (Dosing based on three meals 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 patients have been treated with lanthanum carbonate for more than one year. Long-term safety was demonstrated in patients treated for six years (n=17). 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'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 central nervous system (CNS), gastrointestinal (GI), general products (GP) and human genetic therapies (HGT) - all being areas in which Shire has a commercial presence. 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.
Shire's focused strategy is to develop and market products for specialty physicians. This approach aims to deliver increased returns and lower risks. Shire's in-licensing and merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.
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Statements included herein that are not historical facts are forwarding-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 plc'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, manufacturing and commercialisation; the impact of competitive products, including, but not limited to, the impact of those on Shire plc's Attention Deficit and Hyperactivity Disorder ("ADHD") franchise; patents, including but not limited to, legal challenges relating to Shire plc's ADHD franchise; government regulation and approval, including but not limited to the expected product approval dates of SPD503 (ADHD), SPD465 (ADHD), MESAVANCE(TM) (SPD476) (ulcerative colitis), ELAPRASE(TM) (I2S) (Hunter syndrome) and NRP104 (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire plc's ability to benefit from the acquisition of Transkaryotic Therapies Inc.; Shire plc's ability to secure new products for commercialisation and/or development; and other risks and uncertainties detailed from time to time in Shire plc's and its predecessor registrant Shire Pharmaceuticals Group plc's filings with the US Securities and Exchange Commission, including Shire plc's Annual Report on Form 10-K for the year ended December 31, 2005.
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