Ferinject in NDin ND-CKD - E-Medinfo.e-med.co.il/ferinject/files/2013/05/Nephrology_ND-CKD.pdf ·...
Transcript of Ferinject in NDin ND-CKD - E-Medinfo.e-med.co.il/ferinject/files/2013/05/Nephrology_ND-CKD.pdf ·...
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Ferinject® in ND CKDFerinject® in ND-CKDAn introduction
Vifor Pharma Ltd.a company of the Galenica Group
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Anemia is common in CKDf f Cfrequency increases with severity of CKD
nts)
75.580(%
pat
ien
41.6
53.6
40
60
≤12g
/dl (
26.7
20
40
Hb
01–2 3 4 51 2 3 4 5
CKD stage116 2,832 1,968 298n
McClellan W et al. Curr Med Res Opin 2004; 20: 1501-1510
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Factors contributing to anaemia in CKDg
D dDecreasederythropoietin
productionIron deficiency
(malnutrition)
Aluminiumtoxicity
High hepcidin level
Bloodloss
Inflammation
Anaemia in CKD(eGFR
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CKD, CHF and anemia exacerbate each other
Anemia
Cardio-renal-
anemiaanemia syndrome (CRAS)
Adapted from Besarab A et al Oncologist 2009; 14(Suppl 1): 22 23
CKD CHF
Adapted from Besarab A et al. Oncologist 2009; 14(Suppl 1): 22-23
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Oral iron supplementation
• Easy to administer• Easy to administer• Low cost• Poor absorption from the gastrointestinal tractp g• Gastrointestinal side effects
– CKD stage 3-4 (FeSO4 t.i.d.): constipation 35%, nausea 10%, vomiting 8%, diarrhea 6%1
• Variable compliance• Variable compliance• Interaction with medications• Interaction with food
Charytan C et al. Nephron Clin Pract 2005; 100: c55-c62
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European Best Practice Guidelines recommendationsrecommendations
“ The majority of, if not all, CKD patients will benefit from iron supplementation”
“ Administration of I.V. iron in the absence of ESA therapy may improve anaemia in some renal patients inmay improve anaemia in some renal patients, in particular CKD patients not yet requiring dialysis
“”
“ There is strong evidence from randomised, controlled trials that treatment with I.V. iron is more effective than oral iron in renal failure patients”
Locatelli F et al. Nephrol Dial Transplant 2004; 19(Suppl 2): ii1-ii47
oral iron in renal failure patients
Locatelli F et al. Nephrol Dial Transplant 2004; 19(Suppl 2): ii1 ii47
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The role of iron therapyin managing IDAin managing IDA
• Iron supplementation is recommended for all CKD patients receiving ESA therapy and a C pat e ts ece g S t e apy a dmay delay/avoid the need for ESA therapy
• I.V. iron is more effective than oral iron supplements– Also avoids the disadvantages of oral iron
(poor/variable absorption gastrointestinal(poor/variable absorption, gastrointestinal intolerance, compliance issues)
• Iron supplementation is under-used in ND-ppCKD patients
77
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Iron deficiency is undertreated in ND CKDin ND-CKD
PatientsPatients starting dialysis
ONLY 40%had adequate
iron stores
ONLY 67% of patients who
started ESAiron stores(n=794) ONLY 42% were receiving iron
supplementation
started ESApredialysis
received iron supplementationpp
(n=4,187)supplementation
(n=1,060)
Retrospective data from 1,997 patients starting dialysis 1999-2000 at 779 centres. ESA, erythropoiesis stimulating agent
Valderrábano F et al. Nephrol Dial Transplant 2003; 18: 89-100
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Ferinject® – Breakthrough next generation I V irongeneration I.V. iron
Ferric carboxymaltoseDesigned to overcome current I.V. iron limitations
Unique carbohydrate shell Highly stable, type I iron complex Dextran-free pH 5–7, physiological osmolarity
Low immunogenic potential andiron-induced toxicity
p , p y g y
Rapid and selectivedelivery from plasma to: RES* of the liver RES of the liver Bone marrow
Si l d 1000 Single dose up to 1000 mg No test dose required
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Low risk of immunogenicity and injectionsite reactionssite reactions
No dextran, low risk of immunogenicity with Ferinject
Ferinject does not contain immunogenic triggers
Ferinject does not cross-react with anti-dextran antibodies Ferinject does not cross react with anti dextran antibodies
Ferinject has a near-neutral pH, limiting the likelihood of injection site reactionsreactions
Ferinject osmolarity is comparable to that of blood
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Efficacy is higher with Ferinject® than oral iron
Patients achieving Hb increase ≥1g/dl any time
y g j
during the study (%)
All patients No ESA therapy
p
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Higher serum ferritin levels achieved with Ferinject®Ferinject®
ml) 800
Oral iron (n=141)
*700
Ferinject® (n=144)rit
in (n
g/m
*
700
600
500
*
*
erum
ferr 500
400
300
*
Mea
n se 300
200
100Day 14 Day 28 Day 42 Day 56
*p
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Higher TSAT levels achieved with Ferinject®Ferinject®
36Oral iron (n=141)Ferinject® (n=144)
34
(ng/
ml)
3032
28
an T
SAT
2624
2022
Mea 20
1614
18
Qunibi W et al. ASN 2007. Poster SU-PO1030
Day 14 Day 28 Day 42 Day 5614
Baseline
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Ferinject® increases Hb level without ESA therapy
Patients receiving Ferinject® without
without ESA therapy
ESA therapy (n=111)
11.312
(g/d
l) 10.1
8
10
12H
b le
vel
4
6
8
Mea
n
0
2
4
Baseline Day 56
Benjamin J et al. J Am Soc Nephrol 2009; 20: 666A (SA-PO2422)
0
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Comparable Hb increase with Ferinject®alone versus oral iron with ESA
Ferinject® with ESA use (n=33) Ferinject® no ESA use (n=111)
alone versus oral iron with ESA
100
Oral iron with ESA use (n=24)
*
Oral iron no ESA use (n=77)
with
n or
80
60
*
**
#f sub
ject
s ≥1
g/dl
on
each
vis
it
40 #
#
§
§
§cent
(%) o
fb
incr
ease
be
fore
e *p
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Hb target can be reached in many ND-CKD patients using I V iron without ESApatients using I.V. iron without ESA
/dl (
%)
51 5355
50
60H
b >1
1g/
34
30
40
nts
with
H
20
30
Pat
ien
00
10
Months after start of treatmentMircescu G et al. Nephrol Dial Transplant 2006; 21: 120-124
0 3 6 9 12
Mircescu G et al. Nephrol Dial Transplant 2006; 21: 120 124
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I.V. iron without ESA also significantly improves iron statusimproves iron status
M f iti ( / l)Mean serum ferritin (ng/ml)
443450500
Mean TSAT (%)
33.635
40
*
230259300
350400
21.624.9
26.8 27.8
25
30
35
** * *
*
98
156
230
100150200250
10
15
20
*
* *
050
100
0 3 6 9 120
5
0 3 6 9 12
Months after start of treatment
*p
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I.V. iron may delay or even avoid the need for ESA therapy (1)py ( )
Mean increase in Hb with I.V. iron aloneBenjamin
et al, 20091Tagboto
et al, 20092Tagboto
et al, 20083Mircescu et al,
20064Spinowitz et al, 20085
Mean increase in Hb with I.V. iron alone
Study design
Prospective, open-label,
randomized, multicenter
Retrospective, single-center
Retrospective, single-center
Prospective, single-arm, single-
center
Prospective, open-label, randomized, multicenter
Ti i d 56 d 30 d 28 d 12 th 35 dTime period 56 days 30 days 28 days 12 months 35 daysTherapy Ferinject® Ferinject® Venofer® Venofer® FerumoxytolN 111 30 82 60 145Mean increase in Hb (g/dl)
1.16 0.73 0.53 1.6 0.62
1. Benjamin J et al. J Am Soc Nephrol 2009; 20: 666A (SA-PO2422) 2. Tagboto S et al. J Ren Care 2009; 35: 8-233. Tagboto S et al. J Ren Care 2008; 34: 112-115 4. Mircescu G et al. Nephrol Dial Transplant 2006; 21: 120-124 5 S i it BS t l J A S N h l 2008 19 1599 16055. Spinowitz BS et al J Am Soc Nephrol 2008; 19: 1599-1605
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Fewer adverse events with Ferinject® than oral ironj
Ferinject (n=1968)
10
12
Oral iron (n=834)
O l 1 5% f ti t
6
8
patie
nts
Only 1.5% of patients given Ferinject®-
discontinued due adverse events
0
2
4
a n n e s T scent
age
of p
Nau
sea
Con
stip
atio
n
bdom
inal
pai
n
bdom
inal
pai
n
Dia
rrhea
scol
ored
fece
s
Vom
iting
Hea
dach
e
Diz
zine
ss
crea
sed
seru
mph
osph
orus
ncre
ased
AL T
n-si
te re
actio
ns
Ras
h
Per
c
Ab
Upp
er a Di s
Dec p
I
Inje
ctio
n
Gastrointestinal side effectsLyseng-Williamson KA et al. Drugs 2009; 69: 739-756
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Fewer adverse events with Ferinject® thanoral iron in ND CKD patientsoral iron in ND-CKD patients
Ferinject®(n=147)
Oral iron(n=103)
P value
D l dDrug-related adverse events 2.7% 26.2%
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Ferinject® key messagesj y g
Anemia and iron deficiency are twin burdens facing ND-CKD patientsND CKD patients
Treatment patterns do not reflect guidelines Ferinject® fulfils unmet medical needs Ferinject fulfils unmet medical needs Ferinject® is significantly more efficient than oral iron Ferinject® is well tolerated compared to oral iron Ferinject is well tolerated compared to oral iron Ferinject® offers minimum intervention and maximum
flexibilityflexibility
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Ferinject® – Minimal intervention,maximum impactmaximum impact
High dose drip infusions
single dose up to 1000 mg ironin 15 minutes onlyin 15 minutes onlyno test dose required
500 mg (10 ml)concentration 50 mg iron/ml
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Thank youThank you