Fosrenol(R) Demonstrates Effective Phosphate Control With as Few as Three Tablets a Day (1)

BASINGSTOKE, England, July 18 /PRNewswire/ --

-- New Data Show FOSRENOL Is an Effective Monotherapy - Leading to Improved Phosphate Reduction in Dialysis Patients Previously Receiving Alternative Phosphate Binder Therapies

New data show calcium-free FOSRENOL (lanthanum carbonate) further reduces phosphate levels in dialysis patients previously receiving other monotherapies or combined phosphate binders, including calcium carbonate and sevelamer hydrochloride[1]. The data, presented today at the XLIII ERA-EDTA Congress in Glasgow, also showed that FOSRENOL significantly increased the number of patients achieving Kidney Disease Outcome Quality Initiative (K/DOQI) targets compared to those who were previously treated with other monotherapies.

Dr Alastair Hutchison from the Manchester Institute of Nephrology & Transplantation and one of the trial's lead investigators said, "These study results add further weight to the extensive data package which demonstrates FOSRENOL is an effective phosphate binder. FOSRENOL offers patients with hyperphosphataemia an effective treatment option which could simplify their management by reducing tablet burden to as little as one tablet taken during each meal."

A total of 359 dialysis patients were treated with FOSRENOL as monotherapy and were available for analysis from this multicentre, open label study, following a switch from their previous binder therapy. Over 40% of patients were previously on combination phosphate binder therapy (2 or more binders). The study found that at 12 weeks of FOSRENOL monotherapy, patients' mean serum phosphate levels were 1.84 mmol/L compared with 1.99 mmol/L on other previously received phosphate binding therapies*. In addition, there was an increased percentage of patients who reached KDOQI targets. The study also demonstrated that FOSRENOL was well-tolerated throughout.

(* For patients assessed at Week 12, the mean change from screening to Week 12 was -0.13 (P < 0.05).)

Further data presented at the ERA-EDTA Congress showed that treatment with FOSRENOL was associated with a high level of patient and physician satisfaction, based on a number of assessments and linked to a reduction in tablet burden[2]. The majority of patients and physicians expressed a preference for FOSRENOL over previous phosphate binders.

"Poor patient adherence is a problem often found in patients with hyperphosphataemia," says Dr Rajnish Mehrotra from the Harbor-UCLA Medical Center, California and one of the lead investigators of the trial. "These findings show that FOSRENOL may help to tackle this problem."

Other data presented at the meeting also extended FOSRENOL's existing body of evidence. Data from 93 patients, 17 of whom were followed for up to 6 years in an open-label extension study, showed that FOSRENOL effectively maintained reductions in mean serum phosphate levels whilst remaining tolerated[3].

These studies are promising news for the nearly one million people on dialysis worldwide who are at risk from the serious consequences of hyperphosphataemia, shown to be associated with long-term morbidity and mortality[4]. Up to 70 percent of CKD patients will develop hyperphosphataemia[5] which, if not managed successfully, may cause serious long-term health risks leading to renal osteodystrophy (resulting in bone pain, brittle bones and skeletal deformities), and potentially contribute to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients.[6] As a result, patients with hyperphosphataemia are often already taking as many as eight or nine different medications[7]. As FOSRENOL is associated with a lower tablet burden than existing phosphate binders, it may offer simplified dosing for these patients.

Dr Raymond Pratt, Vice President Shire Global Medical Affairs, said, "Shire welcomes the presentation of these data which further add to the robust evidence supporting the effectiveness and tolerability of FOSRENOL in patients with hyperphosphataemia, as well as showing a high-level of patient and physician satisfaction. Shire is very proud to be able to offer a calcium-free alternative with proven efficacy and tolerability for patients in need of an effective and well-tolerated phosphate binder, which may also help to simplify the management of their condition."

FOSRENOL has been available in the US for 18 months with over 44,000 patients receiving Fosrenol since launch and will continue to be launched across Europe in the remainder of 2006 and into 2007.

Notes to Editors:

Managing Hyperphosphataemia

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 (0.8mmol/L) to 4.5 mg/dL (1.4mmol/L), the blood phosphorus levels of many patients on dialysis exceed 6.5 mg/dL (2.1mmol/L). Such levels have been linked to a significantly higher illness and death risk for patients who have undergone at least one year of dialysis. Most dialysis patients develop hyperphosphataemia.

Hyperphosphataemia disrupts the delicate interplay between the body's levels of calcium, parathyroid hormone (PTH) and vitamin D. Over time, hyperphosphataemia can ultimately lead to calcification of the heart, lung and some arteries. Accumulating evidence shows that hyperphosphataemia 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 5 times greater than that in people aged 65-74 in the general population.[8]

Since dialysis and diet restrictions alone generally cannot control phosphate levels, patients traditionally manage hyperphosphataemia by taking phosphate binding agents with every meal and snack. Such binders "soak up" phosphate in the gastrointestinal tract, before it can be absorbed into the blood. Although these agents can be effective, some can cause potentially serious side effects including hypercalcaemia, bone toxicity and tolerability problems.

Lanthanum carbonate (FOSRENOL(R))

FOSRENOL(R) works by binding to dietary phosphate in the GI tract; once bound, the FOSRENOL(R)/phosphate complex cannot pass through the intestinal lining into the blood stream and is eliminated from the body. As a consequence, overall phosphate absorption from the diet is decreased significantly. Shire has conducted an extensive clinical research programme for FOSRENOL(R) involving over 5500 patients, some of whom have been treated for up to 6 years. This programme has demonstrated that FOSRENOL(R) is an effective phosphate binder with a tolerability profile for long-term use. FOSRENOL(R) was approved by the FDA in October 2004 and is now available for prescription in the US. In March 2005 regulatory authorities in the EU granted marketing authorization for FOSRENOL(R) in sixteen member states, thus completing the first step in securing marketing approval throughout Europe. Fosrenol has since been launched in Ireland, Sweden, Finland, Denmark and Austria. The final step in the European process was recently completed resulting in recommendation for approval in the remaining 11 member states. Further roll-outs are underway across the rest of Europe and other countries around the world. The company has out-licensed the rights to develop, market and sell FOSRENOL(R) in Japan to Bayer Yakuhin Ltd.

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