Bari, 19-20 Marzo 2010
XV Convegno del gruppo di studio di
Dialisi Peritoneale
Francesco Locatelli
Dipartimento di Nefrologia, Dialisi e Trapianto di Rene
Ospedale “Alessandro Manzoni” di Lecco
Erythropoietin has two erythropoietin
receptor binding sites
EPO receptor
EPO receptor
Elliott S, et al. Blood 89: 493-502, 1997
Syed RS, et al. Nature 395: 511-516, 1998
Erythropoietin has two erythropoietin
receptor binding sites
EPO receptor
rHuEPO
EPO receptor
Elliott S, et al. Blood 89: 493-502, 1997
Syed RS, et al. Nature 395: 511-516, 1998
The ideal ESA
 Effective




Safe
Flexible administration route
Less frequent administration schedule
Cheap
Currently available ESAs
 Recombinant human erythropoietin (rHuEPO)
– Epoetin alfa
– Epoetin beta
 Long-acting ESAs
– Darbepoetin alfa
• Different molecular structure
• Increased biological activity
- CERA
• Different mechanism of action
• Different molecular structure
• Increased biological activity
Biochemical and biological properties of
rHuEPO and glycosylation analogs
rHuEPO
3 N-linked carbohydrate chains
Receptor binding
Serum half-life
Biological activity
 Up to 14 sialic acids
 30,400 daltons
 ~40% carbohydrate
4 N-linked carbohydrate chains
 Up to 18 sialic acids
 33,750 daltons
 ~46% carbohydrate
NESP
5 N-linked carbohydrate chains
 Up to 22 sialic acids
 37,100 daltons
 ~51% carbohydrate
Egrie JC, Browne JK. Nephrol Dial Transplant. 2001;16(suppl 3):3-13
Hb concentrations
at 4-week intervals
15
rHuEPO
14
NESP
Hb (g/dL)
13
12
11
10
Patient
numbers:
9
8
rHuEPO
37
35
35
33
34
33
31
129
128
127
127
123
121
106
77
51
1
5
9
13
17
21
25
37
49
NESP
7
Study week
Locatelli F et al. Kidney Int 2001; 60: 741-747
Once week epoetin beta in HD
Mean time-adjusted AUC for haematocrit
• Mean [ 90% CI ]
ITT
PP
- 0.56 [ - 1.22, 0.11 ]
- 0.54 [ -1.27, 0.19 ]
-3
-2
-1
0
1
2
3
Group ratio
Locatelli et al. Am J Kidney Dis 2002, 40: 119-125
Time for Hb to return to 12 g/dL
after dose withheld due to Hb >14 g/dL
rHuEPO (n = 13)
16
NESP (n = 31)
Hb (g/dL)
15
14
13
12
11
10
9
–6 –5 –4 –3 –2 –1
0
1
2
3
4
5
6
7
8
9 10 11
Weeks since withheld dose
Locatelli F et al. Kidney Int 2001; 60: 741-747
DA administration Q2W was not associated
with an increased frequency of Hb >14 g/dL
Mean % of Hb values
> 14 g/dL
Percentage of Hb values >14 g/dL
5
4
2.6
3
2
1.3
1
0
Q2W
QW
(n=153)
(n=153)
Locatelli F et al. Nephrol Dial Transplant 2005;20 S.5:MP181
16 (10) 2007
Serum half life of ESAs
Agent
Epoetin alfa
Epoetin beta
Darbepoetin
alfa
C.E.R.A.
Population
Mean (± SE)
half-life (h)
IV
SC
Healthy volunteers1
6.8 ± 0.6
19.4 ± 2.5
Healthy volunteers1
8.8 ± 0.5
24.2 ± 2.6
Peritoneal dialysis
patients2
25.3 ± 2.2
48.8 ± 5.2
Healthy volunteers3
133 ± 9.8
137 ± 21.9
Peritoneal dialysis
patients4
134 ± 19
139 ± 20
1. Halstenson et al. Clin Pharmacol Ther. 1991:50:702-712
2. Macdougall et al. J Am Soc Nephrol. 1999;10:2392-2395
3. Dougherty et al. ASCO 2004
4. Macdougall et al. ASN 2005
Understanding how C.E.R.A.
is different
Receptor binding
properties
Pharmacokinetic
properties
Different pharmacologic profile
C.E.R.A: Dose independent of schedule
Core study, PP population, n=124 (BA16286)
Mean (SE) change
in Hb (g/dL) at 6 wk
n.s.
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.5
QW
Q3W
Q4W
Administration schedule
Locatelli et al. Curr Med Res Opin 2007;23:969–979
Primary efficacy analysis
C.E.R.A. up to once-monthly as effective as epoetin TIW-QW
Non-inferiority limit:
C.E.R.A. groups vs epoetin
0.004
0.031
PP
ITT
-0.215
-0.213
0.223
0.276
0.025
0.051
-0.220
-0.173
-1.00
-0.75
-0.50
C.E.R.A. Q2W
-0.25
C.E.R.A. Q2W
C.E.R.A. Q4W
Q4W
C.E.R.A.
0.270
0.275
0.00
0.25
0.50
0.75
1.00
Difference in adjusted group mean Hb (g/dL) change
between baseline and evaluation (97.5% CI)
P<0.0001 for all comparisons
Levin NW et al. Lancet 2007, 370 (9596): 1415-1421
IV C.E.R.A. once- and twice-monthly
maintains stable Hb over one year
Mean (SD) Hb (g/dL)
16
C.E.R.A. Q2W IV
15
C.E.R.A. Q4W IV
Epoetin TIW-QW IV
14
13
12
11
10
9
8
7
BL
1
2
3
4
5
6
7
8
9
10 11 12 Final visit
Months
4
8
12 16
20
24
28
32
36
40
Weeks
44
48
52
Levin NW et al. Lancet 2007, 370 (9596): 1415-1421
SC C.E.R.A. once-monthly and twicemonthly as effective as epoetin 3x/wk
PROTOS: primary efficacy analysis (PP population)
Non-inferiority
lower 97.5% CI limit
0.141
- 0.098
C.E.R.A. 1x/2wk
0.380
- 0.022
- 0.262
- 1.00
- 0.75
- 0.50
- 0.25
C.E.R.A. 1x/4wk
0.217
0.00
0.25
0.50
0.75
1.00
Difference in mean adjusted Hb versus epoetin (g/dL)
P < 0.0001 for all comparisons
Sulowicz, Locatelli Clin J Am Soc Nephrol. 2007 Jul;2(4):637-46
Stable Hb maintenance with
once-monthly SC C.E.R.A.
PROTOS: ITT population
Mean (SD) Hb (g/dL)
16
15
14
13
C.E.R.A. 1x/2wk
12
C.E.R.A. 1x/4wk
11
Epoetin 1-3x/wk
10
9
8
7
Months
Weeks
BL
1
2
3
4
5
6
7
8
9
10 11 12 Final visit
4
8
12
16
20
24
28
32
36
40 44
48
52
Sulowicz, Locatelli Clin J Am Soc Nephrol. 2007 Jul;2(4):637-46
IV C.E.R.A. twice-monthly as effective as
darbepoetin 1x/wk
STRIATA: primary efficacy analysis (PP population)
Non-inferiority
lower 95.0% CI limit
0.180
--0.049
0.049
- 1.00
- 0.75
- 0.50
- 0.25
0.00
P < 0.0001
0.408
0.25
0.50
0.75
1.00
Difference in mean adjusted Hb (g/dL)
Canaud….Locatelli et al. ERA - EDTA 2006
Canaud….Locatelli et al. Advance Access Published Nephrol Dial Transplant. 2008 Jul
Stable Hb maintenance with
twice-monthly IV C.E.R.A.
STRIATA: ITT Population
Mean (SD) Hb (g/dL)
16
15
14
13
C.E.R.A. 1x/2wk
12
Darbepoetin 1x/wk
11
10
9
8
7
Months
Weeks
BL
4
1
2
8
3
12
4
16
5
20
6
7
8
9
24
28
32
36
10
11
40 44
12 Final visit
48
52
Canaud….Locatelli et al. ERA - EDTA 2006
Canaud….Locatelli et al. Advance Access Published Nephrol Dial Transplant. 2008 Jul
SC C.E.R.A.: Smooth and steady
Hb increase with a high response rate
ARCTOS: ITT population
Mean (SD) Hb (g/dL)
16
Response
rate (%)
95% CI
C.E.R.A. 1x/2wk
97.5
93.8-99.3
Darbepoetin
alfa 1x/wk
96.3
92.1-98.6
C.E.R.A. 1x/2wk
Darbepoetin alfa 1x/wk
15
14
13
12
11
10
9
8
7
Months
Weeks
BL
1
4
2
8
3
12
4
16
5
20
6 Final visit
24
Macdougall, … Locatelli et al. Clin J Am Soc Nephrol. 2008 Mar;3(2):337-47
Hb concentrations
during 24-week intervals
Locatelli F et al. Kidney Int 2001; 60: 741747
Macdougall, … Locatelli et al. Clin J Am Soc Nephrol.
2008 Mar;3(2):337-47
Mean (SD) Hb (g/dL)
16
15
C.E.R.A. 1x/2wk
Darbepoetin alfa 1x/wk
rHuEPO
14
13
12
11
10
9
8
7
Months
Weeks
BL
1
4
2
8
3
12
4
16
5
20
6
24
Final visit
Fewer patients exceed Hb 13 g/dL with C.E.R.A.
than with darbepoetin alfa
ARCTOS: ITT population
Patients (%)*
40
P < 0.0001
30
20
10
0
C.E.R.A. 1x/2wk
Darbepoetin alfa 1x/wk
*Patients with ≥1 Hb value >13 g/dL during first 8 weeks
Macdougall, … Locatelli et al. Clin J Am Soc Nephrol. 2008 Mar;3(2):337-47
Decline in Hb after withholding treatment
Long C.E.R.A. half-life does not affect Hb decline
following dose interruption – pooled analysis of maintenance studies
Mean (SD) Hb (g/dL)
C.E.R.A. Q4W (n=59)
16
Epoetin (QW to TIW) or
darbepoetin alfa (QW or Q2W)
(n=126)
15
14
13
12
11
10
-3
-2
-1
0
1
2
3
4
5
6
Weeks since treatment interruption
(time 0)
Safety populations
Locatelli F. et al Kidney Intern. S. 2008 : Heifets & Dougherty. WCN 2007
Half life comparison
Methoxy polyethylene glycol-epoetin beta’s
half-life is much longer than that of
darbepoetin alfa
 137 h vs 38 h when given SC
 133 h vs 25 h when given IV
140
SC
IV
Hours
120
100
80
60
40
20
0
Epoetin
alfa
Epoetin
beta
Darbepoetin
alfa
Methoxy polyethlene
glycol-epoetin beta
Halstenson. Clin Pharmacol Ther. 1991;50:702
Macdougall. J Am Soc Nephrol. 1999;10:23925
Reigner. Nephrol Dial Transplant. 2003;18(suppl 4):167 Abstract M527
Half life of epoetins
t ½ (hours)
Intravenous
Subcutaneous
Epoetin alfa
6.8*
3:1
19.4*
Epoetin beta
8.8*
3:1
24.2*
25.3
2:1
48.8
130
1:1
133
75
1:1
~80
Darbepoetin alfa
†
Methoxy polyethylene
glycol-epoetin beta
Hematide
*Healthy volunteers
†Peritoneal dialysis patients
Halstenson. Clin Pharmacol Ther. 1991;50:702
Macdougall. J Am Soc Nephrol. 1999;10:2392
Reigner. Nephrol Dial Transplant. 2003;18(suppl 4):167. Abstract M527
Woodburn. Blood. 2004;104:2904
Ht response to EPO or placebo in PD patients
Nissenson AR et al. J Am Soc Nephrol 5:1517-1529,
1995
Cosa può influenzare la scarsa risposta agli ESAs in DP?
* ERI: EPO resistance
Wei M, et al. Int Urol Nephrol. 2007;39(3):935-40.
ESAs in dialisi peritoneale
• Sono stati condotti pochi trials sull'uso degli
ESA's nei pazienti in dialisi peritoneale
• La via di somministrazione di ESAs in dialisi
peritoneale deve, per ragioni pratiche, essere
SC
• Le dosi di ESAs necessarie per mantenere livelli
di Hb nel range suggerito dalle linee guida in
dialisi peritoneale sono ridotte rispetto ai
pazienti in emodialisi
Once monthly (QM) dosing of darbepoetin alfa was
effective in CKD patients not on dialysis
Open-label study
description*
Treatment +
evaluation
period
Hb study
target
range
Primary
endpoint
Ling1
n=98
Q2W DA → QM DA
29 weeks
10-12 g/dl
% of patients within
Hb study target range
Agarwal2
n=152
Q2W DA → QM DA
33 weeks
11-13 g/dl
% of patients
with Hb ≥11 g/dl
Disney3
n=66
Q2W DA → QM DA
33 weeks
10-13 g/dl
Maintaining mean
Hb ≥10 g/dl
Sousa4
n=71
Q2W DA → QM DA
18 months
11-13 g/dl
Effectiveness and safety
of DA QM
10-12 g/dl
% of patients converting
from EA QW who
preferred DA QM at week 21
Reference
Hoggard5
1Ling
n=442
QW/Q2W rHuEPO →
QM DA
28 weeks
B et al. Clin Nephrol 2005;63:327-34; 2Agarwal AK et al. J Intern Med 2006;260:577-85; 3Disney A et al. Nephrology (Carlton)
2007;12:95-101; 4Sousa American Society of Nephrology 2006; Abstract SA-PO218; 5Hoggard J et al. Curr Med Res Opin
2006;22:2023-30.
Limited evidence with once-monthly dosing
Administration
interval (route of
administration)
Drug
Target Hb
(g/dL)
Population
(no. patients
enrolled)
Trial design
Reference
Epoetin alfa
QW, Q2W
Q3W, Q4W (SC)
≥11
CKD not on
dialysis (n=519)
Randomised
Provenzano
et al 2005
Darbepoetin
alfa
Q4W (SC)
10-12
CKD not on
dialysis (n=97)
Single arm,
non-randomised
Ling et al 2005
Darbepoetin
alfa
Q4W (SC)
≥10
CKD not on
dialysis (n=66)
Single arm,
non-randomised
Disney et al
2007
Darbepoetin
alfa
Q4W (SC)
≥11
CKD not on
dialysis (n=152)
Single arm,
non-randomised
Agarwal
et al 2006
Darbepoetin
alfa
Q3W, Q4W
(IV and SC)
10-13
Dialysis patients
(n=54)
Single arm,
non-randomised
Jadoul et al
2004
a
ESAs, erythropoiesis-stimulating agents; Hb, haemoglobin;
IV, intravenous; SC, subcutaneous
a
Dosing once a month is not indicated for darbepoetin alfa in dialysis, except in Switzerland
Limited evidence of efficacy in HD patients for
once-monthly darbepoetin alfaa
Hb (g/dL)
13.0
Dose (g/wk)
100
Hb
Dose
12.5
Q4W dosinga (n=30)
Q3W dosing (n=44)
80
12.0
522 patients originally
recruited
11.5
60
11.0
40
10.5
10.0
20
9.5
9.0
–2 0
Patients on darbepoetin alfa
Q2W converted to Q3W
dosing and, if Hb stable (1013 g/dL), to Q4W dosinga
0
4
8
12
16
20
26
Study week
30
34
38
42
Limited conversion to Q4W
dosinga:
Of 54 patients entering the
study, 36 patients were
converted to Q4W dosing
Limited maintenance on
Q4W dosinga:
Of 36 patients converting to
Q4W dosing, 30 patients
maintained Hb >10 g/dL over
20 weeks
a
Dosing once a month is not indicated for darbepoetin alfa
in dialysis, except in Switzerland
Jadoul et al. Nephrol Dial Transplant 2004;19:898-903
Labelled dosing information on maintenance
therapy dosing interval
MIRCERA
– Once-monthly maintenance dosing in CKD patients on
dialysis and not on dialysis
Darbepoetin alfa
– In HD patients
Once weekly or once every 2 weeks maintenance dosing
In Switzerland in selected HD patients, also once monthly
– In CKD patients not on dialysis
Stepwise expansion from QW over Q2W to QM for those patients
stable on previous dose interval and by doubling the dose
CKD, chronic kidney disease; HD, haemodialysis; QW,
weekly; Q2W, every 2 weeks;
QM, once monthly
ARANESP, Summary of Product Characteristics, 2006;
MIRCERA, Summary of Product Characteristics, 2007
The PATRONUS study: a
randomised comparison of the
efficacy and safety of MIRCERA®
with darbepoetin alfa using oncemonthly dosing in haemodialysis
patients
PATRONUS study objectives
• Primary
– To compare the efficacy of once-monthly IV MIRCERA®
with that of darbepoetin alfa* in the maintenance of Hb
levels in HD patients with chronic renal anaemia
previously receiving IV darbepoetin alfa maintenance
therapy
• Secondary
– To assess the safety and tolerability of IV MIRCERA® in
HD patients with chronic renal anaemia previously
receiving IV darbepoetin alfa maintenance treatment
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
PATRONUS compared once-monthly MIRCERA®
and darbepoetin alfa maintenance treatment
Evaluation (wk 50-53)
Screening period
MIRCERA®
1x/month
(n=245)
Darbepoetin alfa
1x/week
Primary
end point
R
Darbepoetin alfa
1x/2 weeks
(n=245)
4 weeks
MIRCERA®
1x/month
26 weeks
Darbepoetin alfa*
1x/month
26 weeks
R, randomisation
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
PATRONUS primary end point
• Primary end point: superiority assessment of the
difference in the proportion of responders between
groups
– Responders are patients with an average Hb decrease
from baseline of <1.0 g/dL and an average Hb >10.5 g/dL during
evaluation
• Study was powered to detect an absolute
difference of 15% in the primary end point between
the 2 treatment groups
– Assumed 60% of patients would respond to MIRCERA®
vs 45% to darbepoetin alfa
• Target Hb range: 11–13 g/dL
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Analysis population
• Primary efficacy analysis used the intent-to-treat
population, defined as all randomised patients
– In case of withdrawals, the last Hb value in the second treatment
period was used for the Hb assessment (last value carried forward)
– To correct for any increase in Hb caused by RBC transfusion, the
Hb values measured within 3 weeks after a transfusion were
replaced by the Hb value measured immediately before the
transfusion
• Safety population included all patients who
received >1 dose of MIRCERA® or darbepoetin
alfa
RBC, red blood cell
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Darbepoetin alfa to MIRCERA®
dose conversion schedule
Weekly darbepoetin alfa
dose
(g/week)
MIRCERA® starting dose
(g/month)
<40
120
40–80
200
>80
360
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Darbepoetin alfa starting doses
Two changes needed:
Double Week – 1
dose
Double Week 25
dose
Week 1
4 week
baseline period
26 weeks
Week 27
26 weeks
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
PATRONUS: A multicentre, multinational trial
Country
France
Italy
Spain
Canada
Germany
Belgium
UK
Portugal
Australia
Austria
Switzerland
Finland
Denmark
Total
Patients enrolled
95
86
80
65
33
31
22
21
15
15
11
9
7
490
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Baseline patient characteristics
Male, n (%)
Race, n (%)
Caucasian
Black
Other
Mean age, years (SD)
Mean weight, kg (SD)
Mean baseline Hb, g/dL (SD)
Mean time since first dialysis, years (SD)
MIRCERA®
n=245
Darbepoetin
alfa
n=245
148 (60)
156 (64)
233 (95)
5 (2)
7 (3)
66.2 (13.6)
72.3 (15.1)
12.09 (0.56)
4.20 (5.92)
225 (92)
12 (5)
8 (3)
65.5 (13.9)
73.8 (16.9)
12.07 (0.55)
4.15 (5.55)
30.0 (20-40)
20.0 (15-40)
120.0 (120-200)
100 (60-160)
Dosing
Median darbepoetin alfa dose at week
before randomisation, g (IQR)
Median study drug dose in month 1,
g/month (IQR)
SD = standard deviation; IQR = Interquartile Range
Once-monthly MIRCERA® exhibited a superior
response rate compared with once-monthly
darbepoetin alfa*
Primary end point
*P<0.0001
Response rate (%)
*
64.1%
64.1%
40.4%
40.4%
®
CI, confidence interval
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Once-monthly MIRCERA® shows a 59% higher likelihood of
response compared with once-monthly darbepoetin alfa*
Primary end point
Superiority limit:
MIRCERA® vs darbepoetin alfa
1.59*
1.33
−0.75
*P<0.0001
1.00
1.25
1.90
1.50
1.75
2.0
Relative risk of response at evaluation for
MIRCERA® vs darbepoetin alfa
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Only once-monthly MIRCERA® maintained Hb levels
during the second 26-week treatment period
Evaluation (wk 50-53)
16.0
Median Hb value (g/dL)
15.0
MIRCERA® (median, IQR)
Darbepoetin alfa (median, IQR)
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
Baseline
4
8
12
16
20
24
28
32
Weeks (of trial treatment)
36
40
44
48
52
Darbepoetin alfa dose increased by >30%
during the second 26-week treatment
period
Secondary end point
MIRCERA®
n=211
Darbepoetin alfa
n=219
Week 27
200 (120-313)
150 (80-280)
Months 11 and 12
196 (120-351) 0%
225 (106-400) +35%
Median (IQR) treatment
dose, g/month
• The median MIRCERA® dose was virtually unchanged
during the second 26-week treatment period whereas
darbepoetin alfa substantially increased by 35%
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
MIRCERA® dose was unchanged during the
second 26-week treatment period
Trial treatment dose change
(%)
150
MIRCERA (median, IQR)
Darbepoetin alfa (median, IQR)
125
Secondary end point
100
75
50
25
0
−25
−50
7
8
9
10
11
12
Months (of trial treatment)
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Most safety parameters were similar between
the two PATRONUS study groups
AEs
SAEs
AEs leading to withdrawals
Withdrawals
Withdrawals due to
insufficient response
Deaths*
MIRCERA®, n (%)
n=245
Darbepoetin alfa, n (%)
n=244
222 (90.6)
217 (88.9)
99 (40.4)
94 (38.5)
3 (1.2)
7 (2.9)
58 (23.7)
96 (39.3)
10 (4.1)
48 (19.7)
14 (5.7)
14 (5.7)
*includes 3 patients who died after withdrawal due to other events
AEs, adverse event; SAEs, serious adverse events
• Similar incidence of AEs in both study arms
– higher rate of constipation with MIRCERA®
• Most common AEs in both arms were hypertension (14.7 vs 10.7%),
procedural hypotension (8.6 vs 11.1%) and nasopharyngitis (10.2 vs 8.2%)
• Fewer withdrawals with MIRCERA® than with darbepoetin alfa
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
SAEs (>5% in either group) were comparable
between study groups in PATRONUS
MIRCERA®
n=245
n (%)
Darbepoetin
alfa
n=244
n (%)
All body systems
99 (40.4)
94 (38.5)
Infections and infestations
29 (11.8)
27 (11.1)
Injury, poisoning and procedural
complications
26 (10.6)
18 (7.4)
Cardiac
16 (6.5)
16 (6.6)
Vascular
14 (5.7)
16 (6.6)
Gastrointestinal
11 (4.5)
16 (6.6)
Nervous system
7 (2.9)
13 (5.3)
Neoplasms
10 (4.1)
5 (2.0)
Metabolism and nutrition
10 (4.1)
4 (1.6)
Respiratory, thoracic and mediastinal
4 (1.6)
7 (2.9)
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Clinical Nephrology, Vol 73 – n 2/2010 (94-103)
Conclusions
MIRCERA® was shown to be superior to darbepoetin alfa
as once-monthly treatment in the dialysis setting
– Significantly more patients responded with MIRCERA® compared with
darbepoetin alfa
– MIRCERA® maintained Hb levels within a tight target range during the
second 26-week treatment period
– Mean Hb levels for patients receiving darbepoetin alfa fell to below the
lower target (11 g/dL) over the same 26-week period, despite substantial
dose increases
This is the first large, randomised, prospective head-to-head study that has
shown one ESA to offer superior efficacy compared with another
Carrera F et al. WCN 2009 Milano, poster M558
* Darbepoetin alfa is not licensed for once monthly treatment in dialysis in the UK.
Hb (or at least high levels) vs ESA (or at least high levels)
Hb
ESA