Three efficacy and safety studies supported the approval ofdeferasirox:

  • A randomized comparative study of deferasirox (n=296) vs deferoxamine (n=290) in patients 2 years of age or older (mean age, 17.1 years; range, 2-53 years; 52% female and 88% white) with beta-thalassemia and transfusional hemosiderosis found that deferasirox removed iron from the body in proportion to the amount of the drug administered.24
  • In an open-label, non-comparative trial, deferasirox was given for 1 year to patients with chronic anemias and transfusional hemosiderosis: those with either betathalassemia who could not be properly chelated with deferoxamine (n=85) or with rare anemias requiring chelation therapy (n=99); 19% of patients were <16 years of age and 16% were ≥65 years of age. The primary end point—maintenance or reduction of LIC—was demonstrated with an absolute reduction of -4.2 mg Fe/g dry weight.27
  • In a multicenter, open-label, randomized trial of deferasirox (n=132) vs deferoxamine (n=63) given for 1 year in patients with SCD and transfusional hemosiderosis, the primary objective was to demonstrate safety and tolerability. Adverse events were found to be generally mild to moderate in severity in both groups. Forty-four percent of the patients were <16 years of age.28,30

Other key trials involving deferasirox have continued toexplore its use in patients with beta-thalassemia, SCD, andMDS. For example, the Evaluation of Patient Iron ChelationWith Exjade (EPIC) trial has been the largest prospectivemulticenter study conducted for any iron chelator to date.It included 1744 patients across a number of transfusiondependentanemias. The EPIC study was the first trial toconfirm that fixed starting doses of deferasirox—based onongoing transfusional iron intake, with subsequent dosetitration guided by serum ferritin trends and safety markers—are clinically acceptable for chelation therapy.31 In asubgroup of patients with MDS, deferasirox providedsignificant reduction in serum ferritin levels over 1 year oftreatment, with appropriate dose adjustments every 3 monthsbased on serum ferritin trends and safety markers.32

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Another trial, the 1-year ESCALATOR study, evaluatedthe effects of treatment with deferasirox on LIC in heavilyiron-loaded patients with beta-thalassemia unable to achievesuccessful chelation. When deferasirox doses were adjustedbased on serum ferritin levels and transfusional iron intake,patients maintained or reduced their iron burden as measuredby LIC.33 An additional year of treatment foundoverall safety was maintained.34

Cardiac Efficacy
Several clinical trials have investigated the effect of deferasiroxon cardiac iron loading, cardiac iron removal, andcardiac function, as measured by left ventricular ejectionfraction (LVEF), primarily in patients with beta-thalassemia(Table 3). Myocardial MRI T2* values of <20 ms indicatea progressive and significant decline in LVEF; the lower

TABLE 3. Deferasirox Clinical Trials Measuring Cardiac Efficacy

Removal of Myocardial Iron
1-year cardiac reduction
Heavily transfused patients
with beta-thalassemia and
mild, moderate, and severe
myocardial siderosis (n=114)
30 mg/kg/day
(dose adjustments allowed based
on safety and efficacy monitoring:
5 mg/kg/day-40 mg/kg/day)
Over 12 months of therapy (n=105):

  • Cardiac T2* significantly improved
  • LVEF remained stable
  • Myocardial T2* was inversely correlated
    with LIC

18-month study with 6-month extension36
Iron-overloaded patients with beta-thalassemia (n=26) 30 mg/kg/day (dose adjustments allowed based on safety and efficacy monitoring to 40 mg/kg/day) Over 18 months of therapy (n=12):

  • Cardiac T2* significantly improved
  • LVEF trended upward
  • 83.3% of patients responded (≥4%
    increase in T2*)
  • Patients with both baseline LIC <18.5 mg
    Fe/g dw and cardiac T2* >6 ms showed improvement
    in T2* >1% per month

Baseline cardiac MRI scans prior
to therapy and a follow-up scan
1 to 2 years later37

Patients with thalassemia
major (n=19) were divided
into two groups: baseline cardiac T2* >20 ms or
T2* <20 ms

20 mg/kg/day to 35 mg/kg/day Over a mean treatment period of 488 days:

  • T2* significantly improved in 9 patients with myocardial iron loading and T2* <20 ms
  • In 10 patients with T2* >20 ms, T2* was
    maintained after 2 years
Pooled analysis of a sub-
population of two studies, a phase III
randomized trial of deferasirox vs deferoxamine followed by deferasirox only  for 4 years, and a phase II noncomparative trial38

Patients with transfusion-dependent beta-thalassemia
(n=29) or rare anemias
(eg, MDS, Diamond Blackfan, other) (n=6)

Doses at baseline and 1 year calculated from baseline and 1-year LIC, respectively. Dose adjustment after 1 year based on serum ferritin trends
Mean starting dose:
21 mg/kg/day
(range: 10 mg/kg/day–
30 mg/kg/day)
Mean final dose: 29 mg/kg/day
(range: 7.5 mg/kg/day–
40 mg/kg/day)


Over 4 years:

  • Cardiac T2* significantly improved

  • Mean T2* improved to 0.7 ms (within normal range)

  • Greatest improvement in T2* occurred in the first year of treatment (0.16 ms/month) and least improvement occurred in the final treatment year

  • Median change: 1.27 ms/year LVEF was maintained over 4 years

Prevention of myocardial siderosis

1-year cardiac prevention
Beta-thalassemia major with normal cardiac function and no cardiac iron overload
20 mg/kg/day or 30 mg/kg/day (dose adjustments allowed based on safety and efficacy monitoring) Over 12 months of therapy (n=78):

  • Myocardial iron accumulation was maintained in normal range in patients with T2* ≥20 ms
  • Cardiac function, as measured by LVEF, improved in patients with LVEF in the
    normal range
  • Myocardial T2* was
    inversely correlated with serum ferritin

dw = dry weight; LIC = liver iron concentration; LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging.Sources: Pennell35; Wood36; Reyal37; Garbowski38; Pennell.39

the value, the higher the risk of cardiac dysfunction.40These studies demonstrate that deferasirox is efficaciousin lowering myocardial iron burden in patients with betathalassemiawho have mild, moderate, and severe cardiacsiderosis.35-37 Deferasirox is also efficacious in preventingmyocardial iron accumulation in patients with betathalassemiaand normal baseline myocardial iron levels.39 This highlights the importance of early intervention toprevent disease progression and to avoid future cardiacevents resulting from myocardial siderosis.