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Paricalcitol Gains Indication for the Prevention and Treatment of Secondary Hyperparathyroidism

ABBOTT PARK, Ill., May 27 /PRNewswire-FirstCall/ -- Abbott announced today that the U.S. Food and Drug Administration (FDA) has approved Zemplar(R) (paricalcitol) Capsules, an oral, activated vitamin D therapy for prevention and treatment of secondary hyperparathyroidism (SHPT). Zemplar Capsules are indicated for the prevention and treatment of SHPT in stages three and four chronic kidney disease (CKD) patients, before the need for dialysis or transplantation.

"We are pleased to bring a significant and convenient treatment advance to pre-dialysis patients with secondary hyperparathyroidism in stage three and four chronic kidney disease," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott. "The approval and availability of Zemplar Capsules further demonstrates Abbott's continued commitment to the renal community and our role in addressing the chronic kidney disease epidemic."

SHPT is a major complication associated with CKD that can detrimentally impact bones and other vital organs, including the heart, muscles and nerves if left untreated. It can occur when kidneys lose their ability to activate vitamin D obtained through diet and other sources. One in nine adults in the U.S., or 20 million people have CKD and another 20 million are at risk for developing CKD from underlying causes such as diabetes and hypertension.

"The approval of Zemplar Capsules is good news for millions of people with earlier stages of chronic kidney disease," said Daniel W. Coyne, M.D., associate professor of medicine at Washington University School of Medicine and lead investigator for the Zemplar Capsules Phase III studies. "Until now, physicians have had limited treatment options to manage secondary hyperparathyroidism in earlier-stage CKD patients. Zemplar Capsules represent the opportunity to treat this population with a convenient, safe and effective activated vitamin D therapy."

Zemplar Capsules are a new, oral formulation of Zemplar Injection, which was introduced in 1998 and is the most widely-used activated vitamin D for the prevention and treatment of SHPT among dialysis patients. Zemplar Capsules were designed to reduce parathyroid hormone levels (PTH) with minimal impact on calcium and phosphorus levels in a convenient oral form. Reduction of PTH is a key indicator of treatment efficacy. Clinical trial results show that Zemplar Capsules had minimal impact on calcium and phosphorus levels when compared to placebo.

National Kidney Foundation Guidelines for Secondary Hyperparathyroidism
The National Kidney Foundation guidelines recommend testing for and treating SHPT early in CKD, well before the need for dialysis. Earlier management of CKD and its complications may reduce the devastating consequences of the disease, such as bone loss and cardiovascular events.

Zemplar Capsules Achieved Clinical Targets for Parathyroid Hormone Levels with Minimal Impact on Calcium and Phosphorus
Study results from three Phase III trials showed that Zemplar Capsules are safe and effective in reducing parathyroid hormone (PTH) levels in stage three and four kidney disease patients with SHPT. Ninety-one percent of patients treated with Zemplar Capsules had significant and sustained reduction in PTH levels, compared to only 13 percent of placebo patients, after 24 weeks of therapy. Significant reduction in PTH was defined as achievement of at least two consecutive, greater than or equal to 30 percent reductions in PTH. Additionally, patients had a greater than 30 percent mean reduction in PTH by week nine, with a sustained reduction in PTH noted throughout the remainder of the study.

Zemplar Capsule treatment had minimal impact on calcium and phosphorus levels when compared to placebo. Elevations in blood calcium, phosphorus and urinary calcium values are known treatment-related safety concerns that have been associated with treatment of SHPT in stage three and four CKD patients with activated vitamin D therapy. The incidences of hypercalcemia (defined as two consecutive elevated serum calcium levels) and hyperphosphatemia in patients treated with Zemplar Capsules was similar to placebo. There were no treatment-related adverse events associated with hypercalcemia or hyperphosphatemia in the Zemplar Capsules group. No increases in urinary calcium or phosphorus were detected in patients treated with Zemplar Capsules when compared to placebo.

Phase III Study Results for Zemplar Capsules
Results from the Phase III pivotal trials showed no statistically significant difference in adverse events in patients treated with Zemplar Capsules when compared to placebo.

The Phase III trial data were further analyzed to evaluate consistency with the National Kidney Foundation in the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for calcium and phosphorus targets. Calcium, phosphorus and calcium and phosphorus product (Ca X P) values were maintained within the K/DOQI targets for: calcium (91 percent paricalcitol vs. 95 percent placebo), phosphorus (70 percent paricalcitol vs. 75 percent placebo) and calcium and phosphorus combined (94 percent paricalcitol vs. 96 percent placebo). Maintaining appropriate levels of calcium and phosphorus is critical for the effective management of SHPT. Bone disease is a known complication of SHPT that occurs as the kidneys gradually lose their ability to produce activated vitamin D, which is necessary for bone health.

Phase III clinical trials for Zemplar Capsules included patients in stages three (moderate) and four (severe) of chronic kidney disease, who were treated and evaluated in three prospective, randomized, placebo-controlled, double- blinded studies at multiple centers over a 24-week period. Additionally, this trial represents the largest number of patients studied in the early-stage CKD population with SHPT.

"Abbott is committed to ongoing innovation in the area of chronic kidney disease. The approval of Zemplar Capsules is in line with our commitment to pursue multiple regulatory submissions in 2004 and 2005. It further showcases Abbott's robust pipeline of new drugs with the potential to address many critical health issues, including kidney disease, cancer, arthritis and HIV/AIDS," said William Dempsey, senior vice president, Pharmaceutical Operations, Abbott.

Kidney Disease Is a "Growing Epidemic"
According to the National Kidney Foundation, more than 20 million Americans -- one in nine adults -- have CKD and an additional 20 million are at risk, creating what the National Institutes of Health describes as a "growing epidemic." Two major risk factors for kidney disease are diabetes and hypertension, which account for two-thirds of new cases each year. Minority populations also bear a disproportionate burden. CKD includes five stages. Stage five requires the need for dialysis or kidney transplant.

When kidneys start to fail, they gradually lose their ability to activate the vitamin D they obtain through diet and other sources. As a result, many kidney patients develop SHPT, a serious disorder that causes bone disease and can affect many organs and tissues, including red blood cells, the heart, nerves and muscles. If SHPT is not managed early it can worsen, leading to other related conditions and progression of the underlying kidney disease.

Indication and Important Safety Information -- Zemplar (paricalcitol) Capsules
Zemplar Capsule is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease in stage three and four patients.

The safety profile of Zemplar was similar to placebo. Zemplar is contraindicated in patients with vitamin D toxicity, hypercalcemia, or hypersensitivity to any product ingredient.

PTH, calcium and phosphorus levels should be monitored every three months and more frequently during dosage changes. Dosage titration is required to reach optimum reduction/levels of PTH. Excessive administration of vitamin D compounds, including Zemplar Capsules, can cause oversuppresion of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia and adynamic bone disease. For full prescribing information on Zemplar Capsules visit http://www.zemplar.com/ .

Indication and Important Safety Information -- Zemplar (paricalcitol) Injection
Zemplar Injection is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure or stage five CKD.

Adverse effects with greater than 5 percent frequency with Zemplar Injectable versus placebo, regardless of causality, were nausea (13 percent vs. 8 percent), vomiting (8 percent vs. 4 percent), and edema (7 percent vs. 0 percent). Zemplar is contraindicated in patients with vitamin D toxicity, hypercalcemia, or hypersensitivity to product ingredients. Administration may place patients at risk for hypercalcemia, elevated Ca x P product, and metastatic calcification. For full prescribing information on Zemplar Injection visit http://www.zemplar.com/.

Source: Abbott Laboratories

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