Shire Launches New Trial for First Renal Anaemia Treatment Produced in Human Cell Lines

Shire Launches New Trial for First Renal Anaemia Treatment Produced in Human Cell Lines

October 31, 2006

    BASINGSTOKE, England, Oct. 31 /Xinhua-PRNewswire/ --
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: http://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

    For more information, please contact:

     Jessica Mann
     Media Shire
     Tel: [phone]

     Claire Woods / Marilyn Ewan
     Media PR agents for DYNEPO, Resolute Communications
     Tel: [phone]

SOURCE  Shire PLC