First Patients Enrolled into European Phase III Programme for Potential First in Class Oral Treatment for Anaemia Associated

First Patients Enrolled into European Phase III Programme for Potential First
  in Class Oral Treatment for Anaemia Associated with Chronic Kidney Disease
                                    (CKD)

  PR Newswire

  CHERTSEY, England, March 17, 2014

CHERTSEY, England, March 17, 2014 /PRNewswire/ --

     Roxadustat   could   change   treatment   of   anaemia  
 associated   with   CKD   and   remove   the   need   for  
                           multiple   injections

Astellas Pharma Europe Ltd. today announced that the first European patients
have been enrolled into the global ALPINE programme being conducted in
collaboration with FibroGen, Inc to investigate the safety and efficacy of
roxadustat (also known as ASP1517/FG-4592), a potential new oral treatment for
anaemia in people with chronic kidney disease (CKD). In Europe, Astellas will
conduct three Phase III studies as part of this programme, ALPS, DOLOMITES and
PYRENEES, encompassing both non-dialysis and dialysis patients. Approximately
1,800 patients will be enrolled in Europe and the studies will compare
roxadustat to both current treatment and placebo. Roxadustat is not currently
licensed for use in any country.

Treatments for anaemia aim to raise haemoglobin (Hb) levels in the blood to
help the body transport oxygen more effectively. ^[ ^1 ^] Current treatment
options often involve a combination of injectable ESAs and iron supplements
which can be delivered either orally or intravenously. ^[ ^2 ^] There are some
safety concerns regarding current treatments (known as
erythropoiesis-stimulating agents, or ESAs), which have been shown to increase
blood pressure ^[ ^2 ^] and to be associated with an increased risk of
cardiovascular events when used to target high Hb levels. ^[ ^3 ^] Dosing
guidance for ESAs has been revised as a result of these concerns. ^[ ^4 ^]

In Phase II studies roxadustat was well tolerated, and was seen to correct and
maintain Hb levels in people with anaemia associated with CKD. ^[ ^5 ^] Of key
interest, no increase in blood pressure was detected and there was no need for
additional intravenous infusions of iron (a common requirement associated with
currently used ESAs). ^[ ^5 ^] The ALPINE study programme is being conducted
alongside other global Phase III studies to investigate whether roxadustat can
offer patients with anaemia associated with CKD effective oral treatment
without the need for additional injections or increasing patients'
cardiovascular risk profile.

" For   years   we   have   had   to   give   people   with 
 CKD   two   injections   to   treat   their   anaemia ", said Dr
Ashraf Mikhail, Senior Clinical Tutor at Swansea University and UK
Coordinating Investigator for the ALPS study. " Firstly   we   give  
intravenous   iron,   the   building   blocks   for   haemoglobin,
  and   ESA,   which   processes   these   building   blocks  
into   blood   elements.   This   requires   a   lot   of  
time,   monitoring,   testing   and   patient   visits.  
Roxadustat   could   allow   us   to   replace   all   this  
with   one   tablet,   and   potentially   transfer   management 
 of   this   condition   from   secondary   to   primary  
care. "

Roxadustat is the first compound in a potential new therapeutic class known as
hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (or HIF-PHIs) to
enter Phase III studies. ^[ ^6 ^] Roxadustat raises Hb levels via a mechanism
which mimics the natural effects of high altitude. ^[ ^6 ^] It has long been
known that Hb production increases at high altitude, and HIF promotes
generation of the red blood cells which carry Hb. ^[ ^6 ^] By increasing HIF
levels, roxadustat increases Hb levels through utilising the body's own iron
stores, leading to Hb control without the need for supplementary iron. ^[ ^5
^]

" Roxadustat   has   the   potential   to   change   the  
treatment   of   anaemia   associated   with   CKD " , said Dr
Michael Allen, Therapeutic Area Head, Urology and Nephrology, Astellas Pharma
Global Development. " We   are   very   pleased   to   mark   this
  milestone   in   roxadustat ' s   development,   which   is  
also   an   important   one   for   Astellas.   We   are  
looking   forward   to   working   with   the   nephrology  
community   as   we   establish   ourselves   in   the   area, 
 and   hope   to   make   contributions   similar   to   those
  Astellas   has   made   in   areas   such   as  
transplantation   and   urology. "

Astellas has licensed certain rights to roxadustat from FibroGen in
territories that include Japan, Europe, the Commonwealth of Independent
States, the Middle East, and South Africa. Astellas will be responsible for
regulatory filings to the EMA when appropriate.

CKD is a growing worldwide public health issue ^[ ^7 ^] , and can lead to
patients requiring dialysis. The European Kidney Health Alliance estimate that
over 10% of people in Europe have CKD. ^[ ^8 ^] As CKD gets more severe it is
more likely to cause anaemia, a debilitating condition which can cause fatigue
and breathlessness to the extent that normal daily activities become
challenging or impossible. ^[ ^2 ^] Studies suggest that around 12% of people
with CKD also have anaemia. ^[ ^1 ^] CKD is responsible for a large financial
burden on European healthcare systems, with dialysis alone accounting for up
to around 2% of the European health care budgets, although only a small
proportion (<0.1%) of the population need treatment. ^[ ^9 ^]

About   Anaemia

Anaemia is the condition of having fewer red blood cells and/or lower
haemoglobin levels than is normal. The prevalence of anaemia increases with
the progression of CKD and is a demonstrated risk multiplier in patients with
pre-existing cardiovascular disease. Anaemia has been associated with adverse
outcomes in CKD patients, increased hospitalisation rates, increased
mortality, and reduced quality of life, but the condition tends to be
undertreated due in part to the cost and complexity of treatment with
injectable erythropoiesis-stimulating agents (ESAs) and intravenous iron
supplements.

About   Astellas   Pharma   Europe   Ltd.

Astellas Pharma Europe Ltd., located in the UK, is the European headquarters
of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company
dedicated to improving the health of people around the world through the
provision of innovative pharmaceuticals. The organisation's focus is to
deliver outstanding R&D and marketing to continue growing in the world
pharmaceutical market. Astellas Pharma Europe Ltd. is responsible for 21
affiliate offices located across Europe, the Middle East and Africa, an R&D
site and three manufacturing plants. The company employs approximately 4,300
staff across these regions. For more information about Astellas Pharma Europe,
please visit http://www.astellas.eu .

References

1. Anaemia in Chronic Renal Disease. Information for Healthcare Professionals.
Patient.co.uk. Available online at:
http://www.patient.co.uk/doctor/Anaemia-in-Chronic-Renal-Disease.htm . Last
accessed November 2013

2. Lankhorst CE, Wish JB. Anemia in renal disease: Diagnosis and management.
Blood   Reviews 24 (2010) 39-47. Available online at:
http://www.bloodreviews.com/article/S0268-960X(09)00054-X/fulltext . Last
accessed November 2013

3. Singh et   al . Correction of Anemia with Epoetin Alfa in Chronic Kidney
Disease. New   England   Journal   of   Medicine 2006; 355:2085-98

4. McMurray JJV, Parfrey PS et   al. KDIGO (Kidney Disease - Improving
Global Outcomes) Clinical Practice Guideline for Anemia in Chronic Kidney
Disease. Kidney   International   Supplements VOL 2 | ISSUE 4 | AUGUST (2)
2012, 279; doi:10.1038/kisup.2012.37. Available online at
http://www.nature.com/kisup/journal/v2/n4/index.html . Last accessed November
2013

5. Besarab A et   al. Evaluation of hypoxia-inducible factor prolyl
hydroxylase inhibitor FG-4592 for haemoglobin correction and maintenance in
nondialysis chronic kidney disease patients for 16 and 24 weeks. Abstract
FP215. Nephrology   Dialysis   Transplantation Volume 27: Supplement 2;
page ii144 May 2012. Available online at
http://ndt.oxfordjournals.org/content/27/suppl_2/ii133.full.pdf+html?sid=0a825489-ef30-4c74-b3bb-dee904a54d7e
. Last accessed November 2013

6. Bouche. First-in-class anaemia drugtakes aim at Amgen's dominion. Nature 
 biotechnology 2013; 31:11

7. Zoccali C et   al . Epidemiology of CKD in Europe: an uncertain scenario.
Nephrology   Dialysis   Transplantation (2010) 25: 1731-1733. Available
online at: http://ndt.oxfordjournals.org/content/25/6/1731.full . Last
accessed November 2013

8. The Alarming Rise in Chronic Kidney Disease in Europe. How to deal with
this costly problem. European Kidney Health Alliance. Published online at
http://www.era-edta.org/images/2013_EKHA_Call_to_Action_ANNEX_2%20.pdf . Last
accessed November 2013 

9. Lameire N et   al. Chronic kidney disease: A European perspective. Kidney
  International , Vol. 68, Supplement 99 (2005), pp. S30-S38. Available
online at: http://www.nature.com/ki/journal/v68/n99s/full/4495665a.html . Last
accessed November 2013

Contact: Mindy Dooa, Corporate Communications Director, Astellas Pharma Europe
Ltd., M: +44(0)7826-912339, E: Mindy.Dooa@astellas.com
 
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