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