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Date
Contact
31 August 2015
[email protected]
Subject
Ferinject® (ferric carboxymaltose) in iron deficient heart failure patients: a meta-analysis of individualpatient data from randomised clinical trials shows potential to reduce rate of cardiovascular
hospitalisation and cardiovascular death.
Heart Failure
More than 23 million people worldwide suffer from heart failure (HF), a progressively burdensome
and debilitating condition1 with an increasing incidence and prevalence especially in the elderly (>10%
prevalence).2
Despite advances in HF management, a diagnosis of HF carries a substantial risk of poor outcomes
to include, hospitalisation and mortality; half of all patients diagnosed with HF will die with 4 years.3
HF is responsible for high rates of costly hospitalisations4 and around 1-2% of total healthcare
expenditure in developed countries, with HF hospitalisations representing nearly 70% of these
costs.5 Reducing the risk for cardiovascular hospitalisation and death remain a clinical priority in
CHF.6
Iron Deficiency in Heart Failure
Iron deficiency (ID) is a recognised comorbidity in chronic heart failure (CHF)8 and, in Europe,
present in up to 50% of patients. ID, even in the absence of anaemia, is associated with high
symptom burden, reduced exercise capacity, and impaired quality of life. In addition, ID is an
independent risk factor for mortality.
ID therefore represents a modifiable risk factor where therapeutic intervention could provide benefit
to patients and since 2012, the European Society of Cardiology Heart Failure has recommended the
screening and diagnosis of ID in all patients suspected of having HF, with management a key
component of overall patient care.6 ID is defined as ferritin <100 ng/mL, or ferritin 100-300 ng/mL if
transferrin saturation (TSAT) <20%.
However, ID remains an under-diagnosed and under-treated co-morbidity of HF.7
Meta-analysis Purpose and Design
Although several individual studies have evaluated intravenous (i.v.) iron therapy for ID in CHF, only
studies with i.v. iron as Ferinject® have delivered evidence supporting clinically meaningful
improvements on exercise capacity, symptoms and quality of life.8-13 One of these Ferinject® studies,
CONFIRM-HF, reported an associated reduction in hospitalisations due to HF across 301 patients
when treated with Ferinject® compared to placebo.13
To further characterise Ferinject® benefits on hospitalisation and mortality in ambulatory patients with
systolic CHF and ID, a meta-analysis on individual patient data was performed using all the available
data from 4 completed trials conducted in systolic CHF patients with ID (FER-CARS-01, FAIR-HF,
EFFICACY-HF and CONFIRM-HF) which compared the i.v. iron therapy with Ferinject® with placebo
(saline). This analysis represents data from over 800 ambulatory patients with systolic CHF and ID.
All the trials were designed as double-blind, multi-centre, prospective, randomised trials and enrolled
ambulatory patients with symptomatic CHF (NYHA class II/III) with left ventricular ejection fraction
(LVEF) ≤45% and with the presence of ID (defined as ferritin <100 ng/mL, or ferritin 100-300 ng/mL
if transferrin saturation (TSAT) <20%).
A summary of these trials can be found in Table 1.
The primary efficacy outcome was the composite of all cardiovascular (CV) hospitalisations and CV
deaths. Secondary outcomes included the composites: HF hospitalisation and CV death, CV
hospitalisation and all-cause death and, HF hospitalisation and all-cause death in addition to the
individual composite components. For all four studies, hospitalisations and cause of death were
independently adjudicated in a blinded manner by an adjudication committee.
Ferinject®
Ferinject® (ferric carboxymaltose) is an innovative non-dextran intravenous (i.v.) iron replacement
therapy discovered and developed by Vifor Pharma, a company of the Galenica Group. To date,
Ferinject® has gained marketing authorisation in 68 countries worldwide for the treatment of iron
deficiency where oral iron is ineffective or cannot be used. In many countries, intravenous iron
replacement products are primarily used to treat dialysis patients. However, iron deficiency is also a
complication of many other diseases. Vifor Pharma is evaluating new opportunities in the treatment
of iron deficiency with Ferinject® in different therapeutic areas. Further clinical trials with Ferinject® in
chronic kidney disease (CKD), oncology (anaemia in cancer patients), cardiology (chronic heart
failure), patient blood management and women’s health are ongoing.
FAIR-HF
FER-CARS-01
EFFICACY-HF
CONFIRM-HF
Patient population
Ambulatory, optimally treated,
systolic CHF with ID, NYHA
class II/III
Ambulatory, optimally treated,
systolic CHF with ID, NYHA
class II/III, renal dysfunction
(eGFR< 60ml/min per 1·73m 2)
Ambulatory, optimally treated,
systolic CHF with ID, NYHA
class II/III
Ambulatory, optimally treated,
systolic CHF with ID, NYHA
class II/III
Randomisation
2:1 (FCM:placebo)
1:1 (FCM:placebo)
1:1 (FCM:placebo)
1:1 (FCM:placebo)
Number of patients (FAS)
FCM/Placebo
304/155
30/15
20/14*
150/151
Comparator
i.v. FCM vs. placebo
i.v. FCM vs. placebo§
i.v. FCM vs. placebo
i.v. FCM vs placebo
Study duration
24 weeks
12 weeks
24 weeks
52 weeks
Calculation of iron
repletion dose
Ganzoni formula using the
mean of two baseline Hb
values
Ganzoni formula using the
mean of two baseline Hb
values
Ganzoni formula using the
mean of two baseline Hb
values
Determined by baseline Hb
values and screening body
weight
Correction phase
(i.e. until iron repletion)
Over three to maximally nine
weeks: weekly i.v. injections
(200mg/100mg iron) of
FCM/placebo
For maximally four weeks:
weekly i.v. injections
(200mg/100mg iron) of
FCM/placebo
Over three to maximally nine
weeks: weekly i.v. injections
(200mg/100mg iron) of
FCM/placebo
Over a six week period,
maximally two i.v. injections
(500mg/1000mg iron) of
FCM/placebo
Maintenance phase
4-weekly 200mg iron i.v.
injection (FCM/placebo) up to
24 weeks after randomisation
4-weekly 200mg iron i.v.
injection (FCM/placebo) up to
12 weeks after randomisation
4-weekly 200mg iron i.v.
injection (FCM/placebo) up to
24 weeks after randomisation
3-monthly 500mg iron i.v.
injection (FCM/placebo) up to
36 weeks after randomisation,
if ID still present
Primary endpoint(s)
PGA at Week 24 and NHYA
class from baseline to Week 24
PGA at Week 24 and NHYA
class from baseline to Week 24
Change in 6MWT and NHYHA
class from baseline to Week 24
Change in 6MWT from
baseline to Week 24
Table 1 – Design features of the RCTs included in this meta-analysis
CHF=chronic heart failure. ID= iron deficiency . NYHA=New York Heart Association. eGFR=estimated glomerular filtration rate. FCM=ferric carboxymaltose., IS=iron sucrose. FAS=Full Analysis Set.
i.v.=intravenous. Hb=haemoglobin. PGA=Patient Global Assessment. 6MWT=six-minute walk test. RCT=randomised clinical trial. Ganzoni formula of total iron deficit [mg] = body weight (b.w.) [kg] x (150 actual Hb [g/L]) x 0.24 + 500 [mg]. Iron repletion dose=correction of iron deficiency. * EFFICACY-HF was discontinued due to recruitment issues. § Placebo = i.v. normal saline.
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Vifor Pharma Nordiska AB
Torshamnsgatan 30A • SE-16440 Kista, Sweden
Phone +46 8 558 066 00 • Fax +46 8 558 066 99
www.viforpharma.com
www.viforpharma.com
Vifor Pharma a company of the Galenica Group