New Non-Clinical Data Links DYNEPO(R) (Epoetin Delta) to Reduced Angiogenic Potential

Basingstoke, England, November 5 (ots/PRNewswire) -

- For global distribution excluding the US and Canada

New data presented today at the 40th annual American Society of
Nephrology (ASN) meeting and scientific exposition in San Francisco,
CA, USA, show that epoetin delta - the only
erythropoiesis-stimulating agent (ESA) produced in a human cell line
- has less pronounced angiogenic properties than darbepoetin alfa in
vitro at similar pharmacokinetic concentrations.(1)

Angiogenesis, the formation of new blood vessels from pre-existing
vessels, plays an important role in tumour growth, malignancy and
diabetic retinopathy. The study evaluated the angiogenic potential of
human cell-derived epoetin delta and darbepoetin alfa at broad
concentration ranges using a novel in vitro model that incorporates
key aspects of the complex angiogenesis process.(1)

"Although this research is at a very early stage, this data is the
first step towards evaluating whether different EPO analogues produce
different angiogenic effects," said primary investigator Professor
Alan Stitt, Centre for Vision Science, Queen's University, Belfast,
Northern Ireland, UK. "In the clinical setting, there are situations
where reduced angiogenic potential is beneficial, for example, in
patients with malignancies or proliferative retinopathy. Additional
studies, in both the non-clinical and clinical setting, are needed to
further examine the angiogenic potential and related molecular
mechanisms of epoetin delta."

The authors of the study concluded that the observed
pharmacological effects of epoetin delta and darbepoetin alfa on the
angiogenic response may be associated with their different
glycosylation patterns at clinically relevant doses.(1) Glycosylation
(the process of adding carbohydrate structures to a protein) is
dependent on various factors including species and cell type.(2) As
epoetin delta is produced in human cells by activating the
erythropoietin gene - and all other commercially available ESAs are
presently made in Chinese Hamster Ovary (CHO) cells - epoetin delta
has a different glycosylation pattern to other currently marketed
ESAs.(3)

Neuropathy also commonly develops in people with diabetes who also
suffer from CKD. Additional non-clinical data accepted for
publication at ASN show that in rats, epoetin delta corrects the
reduced nerve conduction velocity (a parameter of nerve function)
associated with neuropathy. This occurred even at doses below those
promoting haematopoiesis.(4)

"This data is particularly interesting," said primary investigator
Professor Norman E Cameron, School of Medical Sciences, University of
Aberdeen, Scotland. "We know that ESAs are effective in correcting
anaemia, but this data suggests that, at least in the non-clinical
setting, epoetin delta may have pleiotropic, non-hematopoietic
effects. Further research is needed to investigate whether structural
differences across ESA analogues influence diabetic co-morbidities,
such as diabetic neuropathy, differently."

To further understand the implications of epoetin delta being
manufactured in a human cell line, Shire is sponsoring a non-clinical
research programme to investigate how epoetin delta affects tissues
and processes outside of the haematopoietic system. Of particular
interest is whether epoetin delta's human cell derivation may
influence co-morbidities of the renal anaemia patient, such as
diabetic complications and vascular disease, in a way that is
different to ESA's derived from animal cells. The research presented
today marks the publication of the first data from the programme.

About DYNEPO

DYNEPO is the first commercially available ESA produced in a human
cell line.(5) This is accomplished by activating the endogenous human
erythropoietin gene in a human cell line using specialised
gene-activating DNA sequences.(6) All other commercially available
ESAs are produced in CHO cells. Anaemic patients with CKD require
treatment with an ESA such as DYNEPO in order to increase red blood
cell production.

DYNEPO is indicated for the treatment of anaemia in patients with
chronic renal failure (CRF) and may be used in patients on dialysis
and in patients not on dialysis.(7)

DYNEPO is a registered trademark of Hoescht GmbH.

(i) While common terminology is now chronic kidney disease (CKD),
some regulatory agencies have not adopted this terminology, instead
they refer to chronic renal failure (CRF); these terms are
essentially interchangeable.

Notes to editors

Shire plc

Shire's strategic goal is to become the leading specialty
biopharmaceutical 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's
in-licensing, merger and acquisition efforts are focused on products
in niche markets with strong intellectual property protection either
in the US or Europe. Shire believes that a carefully selected
portfolio of products with strategically aligned and relatively
small-scale sales forces will deliver strong results.

The "Safe Harbor" Statement Under the Private Securities
Litigation Reform Act of 1995

Statements included herein that are not historical facts are
forward-looking statements. Such forward-looking statements involve a
number of risks and uncertainties and are subject to change at any
time. In the event such risks or uncertainties materialize, Shire's
results could be materially affected. The risks and uncertainties
include, but are not limited to, risks associated with: the inherent
uncertainty of pharmaceutical research; product development
including, but not limited to, the successful development of
JUVISTA(R) (Human TGF beta 3) and GA GCB (velaglucerase alfa);
manufacturing and commercialization including, but not limited to,
the launch and establishment in the market of VYVANSE(TM) (Attention
Deficit and Hyperactivity Disorder ("ADHD"); the impact of
competitive products including, but not limited to, the impact of
those on Shire's ADHD franchise; patents including, but not limited
to, legal challenges relating to Shire's ADHD franchise; government
regulation and approval including, but not limited to, the expected
product approval date of INTUNIV(TM) (guanfacine extended release)
(ADHD); Shire's ability to secure new products for commercialization
and/or development; and other risks and uncertainties detailed from
time to time in Shire plc's filings with the Securities and Exchange
Commission, particularly Shire plc's Annual Report on Form 10-K for
the year ended December 31, 2006.

References

(1) McVicar C, Gardiner T, Stitt A. Human-cell-derived epoetin
delta is less angiogenic than darbepoetin alfa in vitro. Poster
presented at American Society of Nephrology Renal Week, San
Francisco, CA, USA. 2-5 November 2007.

(2) Skibeli V, Nissen-Lie G, Torjesen P. Sugar profiling proves
that human erythropoietin differs from recombinant human
erythropoietin. Blood 2001; 98(13): 3626-3634.

(3) Shahrokh Z, Flatman S, Davies M, et al. Erythropoietin
produced by a human cell line has only trace levels of potentially
immunogenic N-glycolylneuraminic acid residues. Presented at the
European Haematology Association 11th Annual Congress, Amsterdam, The
Netherlands. 15-18 June 2006.

(4) Cameron N and Cotter M. Potential benefits of epoetin delta in
diabetic rats: focus on neuropathy. Abstract accepted at American
Society of Nephrology Renal Week, San Francisco, CA, USA. 2-5
November 2007.

(5) Pratt, R. Epoetin delta for the treatment of anemia in
patients with CKD not requiring hemodialysis. Poster presented at
American Society of Nephrology Renal Week, San Diego, CA, USA; 14-19
November 2006

(6) Deicher R and Hörl W. Differentiating factors between
erythropoiesis-stimulating agents. Drugs 2004; 64(5): 499-509.

(7) DYNEPO Summary of Product Characteristics. Shire
Pharmaceuticals. April 2007.

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

ots Originaltext: Shire Pharmaceuticals Group Plc
Im Internet recherchierbar: http://www.presseportal.de

Contact:
For further information please contact: Investor Relations: Cléa
Rosenfeld +44-1256-894-160, Media Shire: Jessica Mann,
+44-1256-894-280, Media PR agents for DYNEPO: Resolute
Communications, May Baccari, +44-207-357-8187, Media PR agents for
DYNEPO: Resolute Communications, Kirsty Mearns, +44-207-357-8187