NEWS FROM EXJADE  SURVEYS

"Exjade is dosed based on weight with an initial recommended dose of 20 mg/kg/day
 with later adjustments every 3 – 6 months in steps of 5 or 10 mg/kg/day as needed
 to control serum ferritin levels.  In patients at a dose of 30 mg/kg/day with serum ferritin
levels persistently above 2,500 μg/L, doses up to (but not beyond) 40 mg/kg/day may be
 considered.

In an open-label, noncomparative trial of efficacy and safety of Exjade, 184 patients
 (including 47 MDS patients) were treated for up to 1 year at doses of 5, 10, 20,
or 30 mg/kg/day based on baseline liver iron content (LIC).  The reduction in absolute
LIC from baseline to end of study at 1 year was 4.2 mg-Fe/g-dry weight.

In the primary study of Exjade efficacy – an open-label, randomized, active comparator
 study vs.deferoxamine, 586 patients with β-thalassemia and transfusional hemoiderosis
 were randomized with 296 patients receiving Exjade at doses of 5-30 mg/kg/day and
 treated up to 1 year.
 The following figure summarizes the changes in liver iron content and serum ferritin between
 baseline and end of study at 1 year for Exjade patients at doses of 5, 10, 20, and
30 mg/kg/day."

"Gattermann et al. [Haematologica, 2012; 97(9): 1364-1371] have recently published
 data on the impact of chelation therapy with deferasirox (Exjade) on hemoglobin levels,
 platelet counts, and neutrophil counts in patients with transfusion-dependent MDS.
To be included in the trial, patients must have:

1. Been diagnosed with iron overload (serum ferritin > 1,000 μg/L or LIC > 2 mg-Fe/g-dw)
2. Had a history of multiple blood transfusions (> 20 transfusions or > 100 ml/Kg
3.  of RBCs)
4. Not be on a concomitant disease modifying agent for MDS (e.g., Vidaza, Dacogen,
5.  Revlimid)

Recruited patients were treated with deferasirox for 1 year of active treatment – there
was no control arm in the trial design.  The following table summarizes the main study findings:"

	Erythroid analysis	Platelet analysis	Neutrophil analysis
Eligible patients	247	100	50
Inclusion criteria	Pre-treatment HB < 11 g/dl, OR RBC transfusion requirements > 4 units per 8 weeks	Pre-treatment platelets < 100 x 109/L	Pre-treatment ANC < 1.0 x 109/L
Definition of response	HB increase > 1.5g/dL, OR reduction of ≥ 4 RBC transfusions per 8 weeks	Increase > 30 x 109/L for patients below 20 x 109/L, or > 100% increase	> 100% increase, AND absolute increase > 0.5 x 109/L
Response rate	21.5%	13%	22%
Median days to response	109	169	226
Mean actual deferasirox dose, mg/kg/day	~19.3	~19.5	~18.8