Studies Show Patients Switched to Every-Two-Week Dosing With
Aranesp Achieve Stable Haemoglobin Levels and
Receive Fewer Injections
Amgen (Nasdaq:AMGN), the world's largest biotechnology company,
today announced new trial results from two studies,(1)(2) showing that
Aranesp(R) (darbepoetin alfa) administered every two weeks (Q2W) is an
effective treatment for chronic kidney disease (CKD) anaemia patients
in European dialysis settings. The data were presented today at the
2006 European Renal Association - European Dialysis and Transplant
Association Congress (ERA-EDTA). One of these studies formed the basis
for a European Medicines Agency (EMEA) Aranesp label update in Europe
earlier this year. This label update offers the benefit of switching
to Aranesp Q2W from any recombinant human erythropoietin (rHuEPO)
dosing regimen without requiring a dose increase.
"For patients with anaemia associated with chronic kidney disease,
achieving stable haemoglobin levels within the target range as
recommended by the European Best Practice Guidelines is an important
goal," said Fernando Carrera, MD, Eurodial Dialysis Clinic, Leiria,
Portugal. "The results presented today are good news for patients and
physicians as the Aranesp every two week dosing regimen means this
goal can be achieved with less frequent injections. This can help to
improve operational efficiency in dialysis centres."
The results showed the Aranesp Q2W was as effective as Aranesp
once weekly (QW) or other rHuEPO QW in maintaining haemoglobin (Hb)
stability in the normal range (Hb 10-13 g/dL), with no evidence of
overshooting Hb target or increased risk of adverse events.(1)
"Aranesp is the only erythropoietin stimulating agent available in
Europe that offers the treatment option of every two week IV dosing
for all haemodialysis patients," said William Sheridan, MD, vice
president, medical affairs, Amgen International.
"Amgen remains committed to improving the lives of chronic kidney
disease patients and is delighted that the EMEA has recognised the
importance of this new data and labelling to offer a new option to the
Aranesp dosing regimen."
With nearly two million patients treated with Aranesp worldwide,
Amgen continues its commitment to improving the lives of patients with
CKD through meaningful offerings, such as label updates and an
extensive Phase 3 clinical trials programme to study the effect of
treating anaemia or CKD complications in different patient
populations. At ERA-EDTA today, Amgen also announced EVOLVE
(EValuation Of Cinacalcet HCI Therapy to Lower CardioVascular
Events)(TM), the first international, prospective clinical outcomes
study designed to determine whether treating secondary
hyperparathyroidism (HPT) with Mimpara (cinacalcet HCl) can
effectively reduce the risk of mortality and cardiovascular morbidity
in patients undergoing maintenance dialysis. Amgen recently announced
the initiation of the large-scale Phase 3 RED-HF (Reduction of Events
with Darbepoetin alfa in Heart Failure) Trial(TM) that will evaluate
the effect of treatment of anaemia with Aranesp on morbidity and
mortality in patients with symptomatic heart failure. Amgen continues
its ongoing TREAT (Trial to Reduce cardiovascular Events and Aranesp
Therapy) trial in diabetic patients with CKD and anaemia not requiring
dialysis.
About the Phase 3 Data Presented at ERA-EDTA
This 30-week Phase 3 multicentre, double-blind study of 308
haemodialysis patients compared the safety and efficacy of Aranesp Q2W
and QW following a switch from rHuEPO. (2) Patients treated with
rHuEPO were randomised to switch to either Aranesp Q2W or Aranesp QW
for 24 weeks, and Hb and dose were reassessed during weeks 25-30.
Results showed that Aranesp Q2W and QW were comparable in maintaining
Hb with no dose increase after switching from rHuEPO. Additionally,
Aranesp Q2W was not associated with an increased frequency of Hb
greater than 14 g/dL, a level associated with vascular risk, nor was
there a difference in the incidence of vascular disorders or
cerebrovascular accidents between the two arms.
The investigators concluded that Aranesp Q2W keeps haemodialysis
patients within their target range, with no evidence of an increase of
overshooting Hb target or increased risk of adverse vascular events.
Additional Aranesp Data Presented at ERA-EDTA
In another study, 105 haemodialysis patients (41 percent female,
mean age 64.4 years) were followed for 12 months.(1) During the first
six months, they received Aranesp QW, and were switched to receive
Aranesp Q2W for the second six months. The investigators found that
switching dose regimen resulted in no significant differences in mean
haemoglobin levels (P = 0.8) or in mean weekly dose of Aranesp (P =
0.3). They concluded that a switch from Aranesp QW or Q2W maintained
efficacy in stabilising Hb levels without the need for increased
dosing.
About CKD and Anaemia
According to recently published research, around ten percent of
Europeans suffer from CKD,(3) an irreversible condition characterised
by kidney damage and impaired function that often progresses over
time. Patients with CKD often suffer from serious complications such
as anaemia, which occurs when failing kidneys no longer produce
sufficient erythropoietin, a hormone that stimulates the production of
oxygen-carrying red blood cells (RBCs). RBCs contain Hb, a red,
iron-rich protein that carries oxygen from the lungs to all of the
body's tissues. Oxygen provides the energy the body needs for normal
activities. Anaemia occurs when the number of RBCs (or the Hb in them)
falls below normal. Anaemia is defined by the World Health
Organisation (WHO) and European Best Practice Guidelines (EBPG) as
Hb less than 12 g/dL in women and Hb less than 13 g/dL in men.
About Aranesp(R) (darbepoetin alfa)
Aranesp is a recombinant erythropoietic protein (a protein that
stimulates production of red blood cells, which carry oxygen). Amgen
revolutionised the treatment of anaemia with the development of
recombinant erythropoietin, Epoetin alfa. Building on this heritage,
Amgen developed Aranesp, a unique erythropoiesis stimulating protein,
which contains two additional sialic acid-containing carbohydrate
chains compared to the epoetin alfa molecule and remains in the
bloodstream longer than epoetin alfa as demonstrated by its longer
half-life.(4)
Aranesp was granted marketing authorisation by the European
Commission in 2001 for the treatment of anaemia associated with
chronic renal failure in adults and paediatric subjects 11 years of
age or older. Approval was granted in 2004 for an extended dosing of
up to once monthly for the treatment of anaemia in CKD patients not on
dialysis. In 2006, the Aranesp label was updated to allow CKD patients
on dialysis to switch from rHuEPO one to three times a week to Aranesp
every two weeks.
Aranesp is contraindicated in patients with uncontrolled
hypertension. Erythropoietic therapies may increase the risk of
thrombotic events and other serious events.(5) The target haemoglobin
should not exceed 14 g/dL. If the Hb increase exceeds 2.5 g/dL in any
four-week period, dose reductions are recommended.
Pure red cell aplasia (PRCA) caused by neutralising
anti-erythropoietin antibodies has been reported in association with
erythropoietin therapy. These antibodies have been shown to
cross-react with all erythropoietic proteins, and patients suspected
or confirmed to have neutralising antibodies to erythropoietin should
not be switched to Aranesp.
The most commonly reported side effects in clinical trials were
headache, hypertension, injection site pain and thrombosis of vascular
access.(6)
About Amgen
Amgen discovers, develops and delivers innovative human
therapeutics. A biotechnology pioneer since 1980, Amgen was one of the
first companies to realise the new science's promise by bringing safe
and effective medicines from lab, to manufacturing plant, to patient.
Amgen therapeutics has changed the practice of medicine, helping
millions of people around the world in the fight against cancer,
kidney disease, rheumatoid arthritis, and other serious illnesses.
With a broad and deep pipeline of potential new medicines, Amgen
remains committed to advancing science to dramatically improve
people's lives.
Forward-Looking Statement
This news release contains forward-looking statements that involve
significant risks and uncertainties, including those discussed below
and others that can be found in Amgen's Form 10-K for the year ended
December 31, 2005, and in Amgen's periodic reports on Form 10-Q and
Form 8-K. Amgen is providing this information as of the date of this
news release and does not undertake any obligation to update any
forward-looking statements contained in this document as a result of
new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results
may differ materially from those we project. Discovery or
identification of new product candidates or development of new
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and become a
commercial product. Further, preclinical results do not guarantee safe
and effective performance of product candidates in humans. The
complexity of the human body cannot be perfectly, or sometimes, even
adequately modeled by computer or cell culture systems or animal
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(1)Carrera F, Oliveira L, Maia P, Mendes T, Ferreira C. Aranesp
(darbepoetin alfa) administered once every two weeks (Q2W)
maintains recommended haemoglobin (Hb) in chronic kidney disease
(CKD) patients on haemodialysis switched from weekly (QW) dosing.
Abstract presented at XLIII European Renal Association's European
Dialysis and Transfusion Association Congress (ERA-EDTA). 15-18
July 2006; Glasgow, UK.
(2)Locatelli F, Backs W, Del Pino MD, et al. Control of anemia with
Aranesp(R): Hb stability achieved with fewer patients requiring
dose adjustments after switching to Aranesp(R) every two weeks.
Abstract presented at XLIII European Renal Association's European
Dialysis and Transfusion Association Congress (ERA-EDTA) congress.
15-18 July 2006; Glasgow, UK.
(3)De Zeeuw D, Hillege HL, de Jong PE. The kidney, a cardiovascular
risk marker, and a new target for therapy. Kidney Int Suppl 2005;
98: S25-S29.
(4)Macdougall IC, Gray SJ, Elston O, et al. Pharmacokinetics of novel
erythropoiesis stimulating protein compared with epoetin alfa in
dialysis patients. J Am Soc Nephrol 1999; 10: 2392-2395.
(5)Aranesp summary of product information
(6)Aranesp Prescribing Information;
http://www.aranesp.com/pdf/aranesp_PI.pdf.
Last accessed: 27 June 2006.
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