BASINGSTOKE, England, November 5 /PRNewswire/ --
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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.
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'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.
(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.
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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