Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis.
OBJECTIVE
This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis.


METHODS
The FDA reviewed findings of a controlled, open-label, randomized multicenter phase III study of deferasirox vs. deferoxamine in 586 patients with beta-thalessemia and transfusional hemosiderosis. The study results as well as the results of the FDA review of chemistry, preclinical pharmacology, and supportive studies are described.


RESULTS
Following 48 weeks of treatment in the phase III study, patients' liver iron concentrations (a key endpoint variable) had decreased an average of 2.4 mg of iron (Fe)/g dry weight (dw) and 2.9 mg Fe/g dw in the deferasirox and deferoxamine groups, respectively, despite continued blood transfusions in both cohorts. Deferasirox was associated with serum creatinine increases in approximately a third of patients. Common adverse events included gastrointestinal symptoms and skin rash. Other data provided supportive evidence of deferasirox safety and efficacy.


CONCLUSIONS
The FDA granted deferasirox accelerated approval on November 2, 2005, for use in treating chronic iron overload due to transfusional hemosiderosis in patients > or =2 years of age. The sponsor must obtain clinical data demonstrating the drug's long-term safety and effectiveness.
Shashaty
George
G
Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring, Maryland 20993, USA.
Frankewich
Raymond
R
Chakraborti
Tamal
T
Choudary
Jasti
J
Al-Fayoumi
Suliman
S
Kacuba
Alice
A
Castillo
Sonia
S
Robie-Suh
Kathy
K
Rieves
Dwaine
D
Weiss
Karen
K
Pazdur
Richard
R
D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000627:therapeutic use*; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003676:Deferoxamine / Q000627:therapeutic use; D005260:Female; D006486:Hemosiderosis / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D017262:Siderophores / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy*
D001565:Benzoates; D007502:Iron Chelating Agents; D017262:Siderophores; D014230:Triazoles; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox