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New Analyses Demonstrate Positive Effect on Bone With FOSRENOL(R) Treatment Compared With Standard Therapy

Shire PLC
2006-11-20 13:11 1686

Further Data Support the Contribution of FOSRENOL(R) (lanthanum carbonate) to

the Overall Renal Health of the ESRD Patient While Reducing Mean Phosphate

Levels to Within Guideline Targets

BASINGSTOKE, England and SAN DIEGO, Nov. 20 /Xinhua-PRNewswire/ -- New

data presented on Friday 17th November at the American Society of Nephrology

(ASN) Annual Meeting, show FOSRENOL is an effective phosphate binder with a

similar efficacy profile to standard therapy(1). The 2 year data demonstrate

that patients treated with FOSRENOL showed similar phosphate control and

lower serum calcium levels than standard therapy. Treatment with FOSRENOL for

2 years had no adverse effects on bone histology and was not associated with

an increased incidence of osteomalacia (bone softening). More patients

treated with FOSRENOL also demonstrated increases in bone formation rate than

patients receiving standard therapy(1).

Professor Hartmut Malluche, lead investigator of the study,

said "Patients with end-stage renal disease are seriously ill and the burden

of their illness is often compounded by co-existing conditions. They can

experience significant bone problems as a result of hyperphosphataemia, which

can sometimes be exacerbated by their treatment for the condition. These data

show that FOSRENOL not only effectively controls hyperphosphataemia, but also

demonstrates some positive effects on bone status compared with standard

therapy over the 2 year study period."

During year two, a greater proportion of patients in the standard therapy

group showed movement of bone volume away from the normal range compared with

the FOSRENOL group (50 percent versus 31 percent). Similarly, improvements

toward normal bone formations rates were seen in 38 percent of patients

receiving FOSRENOL at both one and two years. Patients in the standard

therapy group showed improvements of only 24 and 12 percent at one and two

years, and bone formation worsened in 63 percent of the patients in the two-

year group(1). The results were not measured for statistical significance.

FOSRENOL’s therapeutic profile is further reinforced by the publication

of new cognitive function data in Kidney International this month(2). This

data assessed the comparative cognitive decline in dialysis patients taking

FOSRENOL and standard therapy to control phosphate levels. Cognitive decline

is a significant problem in this population and it is important that any

treatment does not affect this further. These long term two year data show

that FOSRENOL does not adversely affect the decline of cognitive function

compared to standard therapy(2). There is a paucity of evidence looking at

cognitive function in this patient population and this study provides

important additional insight into the overall decline in cognitive function

in these patients.

Dr Raymond Pratt, Vice President Shire Pharmaceutical Development,

said: "These results further add to the robust body of evidence on FOSRENOL,

with studies successfully conducted in more than 5,500 patients, and with a

small number followed for up to 6 years now. Shire is proud of this

comprehensive data which support the benefits FOSRENOL can bring to patients

with CKD on dialysis."

These studies are promising news for the estimated 1.4 million people on

dialysis worldwide(3) who are at risk from the serious consequences of

hyperphosphataemia, shown to be associated with long-term morbidity and

mortality(4). The majority of CKD patients will eventually develop

hyperphosphataemia(5) which, if not managed successfully, may cause serious

long-term health risks including renal osteodystrophy (resulting in bone

pain, brittle bones and skeletal deformities)(6), and potentially contribute

to cardiovascular disease, which accounts for almost half of all deaths among

dialysis patients(7,8). As a result, patients on dialysis are often already

taking as many as eight or nine different medications(9). As FOSRENOL is

associated with a lower tablet burden than existing phosphate binders (as few

as one pill per meal), it may offer simplified dosing for these patients(10).

FOSRENOL has been available in the US for 22 months with over 53,000

patients receiving Fosrenol since launch. The first European launches took

place at the end of 2005 and Shire continues to bring Fosrenol to market

around the world across this year and into 2007, subject to national

licensing, pricing and reimbursement negotiations.

References

(1) Malluche HH, Pratt RD. Renal osteodystrophy: Comparison of

evolution over 1 and 2 years during treatment with lanthanum

carbonate or standard phosphate binders. Presented at ASN Renal

Week, San Diego, November 14-19 2006.

(2) Altman P, Barnett ME, Finn WF. Cognitive function in stage 5 CKD

patients on hemodialysis: no adverse effects of lanthanum

carbonate compared with standard phosphate-binder therapy.

Kidney Int advance online publication, October 11, 2006

(3) Grassman A, Gioberge S, Moeller S, Brown G. ESRD patients in

2004: global overview of patient numbers, treatment modalities

and associated trends. Nephrol Dial Transplant 2005; 20:

2587-2593.

(4) Block G, Klassen PS, Lazarus MJ, Ofsthun N, Lowrie EG, Chertow

GM. Mineral metabolism, mortality, and morbidity in maintenance

hemodialysis. J Am Soc Nephrol 2004; 15:2208-18.

(5) Lederer E, Ouseph R, Erbeck K. Hyperphosphataemia.

http://www.emedicine.com/med/topic1097.html . Accessed

23-Mar-06.

(6) Martin K, Gonzalez A. Strategies to minimize bone disease in

renal failure. Am J Kidney Dis 2001; 38: 1430-36

(7) Salusky IB, Goodman WG. Cardiovascular calcification in

end-stage renal disease. Nephrol Dial Transplant 2002; 17:

336-339.

(8) Block G, Port FK. Re-evaluation of risks associated with

hyperphosphataemia and hyperparathyroidism in dialysis patients:

recommendations for a change in management. Am J Kidney Dis

2000; 35 (6): 1226-1237.

(9) United States Renal Data System. Medication use among dialysis

patients in DMMS. Am J Kidney Dis 1998; 32 (2) Suppl 1 (August):

S60-68.

(10) Mehrotra R. Efficacy and safety of reformulated higher dosage

lanthanum carbonate. Presented at ASN Renal Week, San Diego,

November 14-19 2006.

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(i). 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(ii). Accumulating evidence shows that hyperphosphataemia

contributes to cardiovascular disease, which accounts for almost half of all

deaths among dialysis patients(iii). 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(iv).

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.

FOSRENOL(R) (lanthanum carbonate)

FOSRENOL(R) works by binding to dietary phosphate in the GI tract; once

bound, the lanthanum/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 involving over 5500 patients, with a small number followed for

up to 6 years now. This programme has demonstrated that FOSRENOL is an

effective phosphate binder with a good tolerability profile for long-term

use. FOSRENOL 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 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 in Japan to Bayer Yakuhin Ltd.

Patients with renal insufficiency may develop hypocalcaemia. Serum

calcium levels should therefore be monitored at regular time intervals for

this patient population and appropriate supplements given.

No data are available in patients with severe hepatic impairment.

Caution should, therefore, be exercised in these patients, as elimination of

absorbed lanthanum may be reduced.

FOSRENOL should not be used during pregnancy.

Patients with acute peptic ulcer, ulcerative colitis, Crohn’s disease or

bowel obstruction were not included in clinical studies with Fosrenol.

The most commonly reported Adverse Drug Reactions (ADRs) (>1/100, 1/10)

are gastrointestinal reactions such as abdominal pain, constipation,

diarrhoea, dyspepsia, flatulence, nausea and vomiting. These are minimized

by taking FOSRENOL with food and generally abated with time with continued

dosing. Hypocalcaemia was the only other commonly reported adverse reaction.

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 attention deficit and

hyperactivity disorder (ADHD), 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.

For further information on Shire, please visit the Company’s website:

http://www.shire.com .

(i) Block GA et al. Association of serum phosphorus and calcium x

phosphate product with mortality risk in chronic hemodialysis

patients: A national study. American Journal of Kidney Diseases

1998; 31: 607-617

(ii) Norris KC. Toward a new treatment paradigm for

hyperphosphataemia in chronic renal disease. Dialysis &

Transplantation 1998; 27 (12): 767-773

(iii) Block G, Port FK. Re-evaluation of risks associated with

hyperphosphataemia and hyperparathyroidism in dialysis

patients: recommendations for a change in management. Am J

Kidney Dis 2000; 35 (6): 1226-1237

(iv) Foley R et al. Clinical epidemiology of cardiovascular disease

in chronic renal disease. American Journal of Kidney Disease

1998; 32 (5) Suppl 3:112-119

Source: Shire PLC
collection