Asia PR News

BASINGSTOKE, Oct. 31 /PRNewswire-AsiaNet/ –

Shire today announced the start of a new Phase IIIb clinical trial to
evaluate two new dosing schedules of DYNEPO(R) (epoetin delta), the first
commercial erythropoiesis-stimulating agent produced in a human cell line.
DYNEPO is used in the treatment of anaemia in patients with chronic kidney
disease (CKD[*]). Anaemia becomes more common and severe as a patient’s kidney
function declines.(1)

Patients with anaemia have reduced haemoglobin levels. DYNEPO has
previously been shown to be as effective as epoetin alfa in increasing and then
maintaining haemoglobin levels in the target range (10-12 g/dL) in patients
with anaemia associated with CKD when initially given three times per week by
the intravenous route.(2,3) It is also effective when given twice per week via
the subcutaneous route.(3,4) This open-label, randomised study will investigate
the efficacy and safety profiles of different starting doses of DYNEPO
administered by subcutaneous injection, which are at a lower frequency (once
weekly and once every two weeks) than those currently approved for subcutaneous
administration.

The study is planned to enroll over 400 patients with anaemia and CKD, who
are either not on dialysis, who require peritoneal dialysis or who require
haemodialysis, at over 50 centres across Europe. It will include patients
suffering from kidney disease as a result of diabetes (diabetic nephropathy).

The primary endpoints of the study are to:

- assess whether DYNEPO administered once per week is as effective as
when administered twice per week for patients who have not previously
been treated with an erythropoiesis-stimulating agent (this will be
assessed by measuring haemoglobin levels at Week 24).

- assess whether DYNEPO administered once every two weeks is as effective
as when administered once per week for patients who have been previously
treated with another erythropoiesis-stimulating agent (this will be
assessed by measuring haemoglobin levels over Weeks 16 to 24).

Dr Iain Macdougall, lead investigator of the study and Consultant
Nephrologist and Honorary Senior Lecturer from the Renal Unit in King’s College
Hospital, London commented, "If the study demonstrates the efficacy of the
different dosing schedules of DYNEPO, it will allow future flexibility in the
frequency of subcutaneous administration of the product. An interesting
secondary endpoint of this study is to also monitor diabetic retinopathy, the
progressive damage to the eye’s retina, in those patients with anaemia,
diabetes and CKD."

CKD is a progressive condition that results in end stage renal disease
(ESRD). Approximately 1.8 million people worldwide are undergoing treatment for
ESRD, of whom approximately 77% are on dialysis.(5) In Europe, the prevalence
of ESRD is estimated at 225,000, growing at 6 per cent per annum.(6)

"This new trial demonstrates Shire’s continuing commitment to the care of
people suffering from CKD and ESRD," commented David Milton, Senior Vice
President, Renal Business Unit Leader, Shire.

ABOUT DYNEPO
Erythropoietin is normally produced in the kidneys and stimulates the bone
marrow to produce more red blood cells by promoting the development of stem
cells into mature red blood cells. Red blood cells (erythrocytes) contain
haemoglobin and are vital for oxygen transportation around the body. If the
kidney starts to fail, natural production of erythropoietin declines leading to
lower levels of haemoglobin (anaemia). DYNEPO is the first
erythropoiesis-stimulating agent produced by gene-activation technology in a
human cell line; all others are produced in animal cell lines — either Chinese
Hamster Ovary Cells or baby hamster kidney cells. Anaemic patients with CKD
require treatment with an erythropoiesis-stimulating agent such as DYNEPO in
order to increase red blood cell production. Currently DYNEPO is given twice
weekly if administered via the subcutaneous route, and three times per week if
administered intravenously.

Notes to Editors

SHIRE PLC
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 attention deficit and hyperactivity disorder (ADHD),
human genetic therapies (HGT), gastrointestinal (GI) and renal diseases. 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. 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.

For further information on Shire, please visit the Company’s website:
www.shire.com

References

(1) Locatelli F, Alijama P, Barany P et al. Revised European Best
Practice Guidelines for the management of anaemia in patients with
chronic renal failure. Section 1: Anaemia evaluation. Nephrol Dial
Transplant 2004a; 19 Suppl 2: ii2-ii5.

(2) M Smyth, KJ Martin, RP Pratt. Epoetin delta (Dynepo(R)),
erythropoietin produced by a human cell line, is as effective as
epoetin alfa in patients with renal anaemia, including those with
diabetic nephropathy. Poster presented at the 42nd Annual Meeting of
the European Association for the Study of Diabetes (EASD), 14-17
September 2006, Copenhagen-Malmoe, Denmark-Sweden.

(3) DYNEPO Summary of Product Characteristics (SPC). 8 June 2006. Shire
plc. Available at URL:
http://www.emea.eu.int/humandocs/PDFs/EPAR/dynepo/H-372-PI-en.pdf.

(4) JTC Kwan, M Smyth, RD Pratt. Human cell line derived erythropoietin
(epoetin delta, Dynepo(R)) administered subcutaneously is effective
in the management of anaemia associated with chronic kidney disease.
Poster presented at the 42nd Annual Meeting of the European
Association for the Study of Diabetes (EASD), 14-17 September 2006,
Copenhagen-Malmoe, Denmark-Sweden.

(5) Grassmann A, Gioberge S, et al. ESRD patients in 2004: global
overview of patient numbers, treatment modalities and associated
trends. Nephrol Dial Transplant 2005; 20: 2587-2593.

(6) Molowa DT. First annual nephrology survey. With a focus on Aranesp
and Renagel. J.P.Morgan Securities Inc. Equity Research. 13 February
2002.

[*] CKD is sometimes referred to as chronic renal failure

SOURCE: Shire PLC

CONTACT: For further information please contact:

Media Shire,
Jessica Mann,
+44-1256-894-280;

Media PR agents for DYNEPO,
Resolute Communications,
Claire Woods,
+44-207-357-8187;

Media PR agents for DYNEPO,
Resolute Communications,
Marilyn Ewan,
+44-207-357-8187

Web site: http://www.shire.com