A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia.
Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n = 296) or deferoxamine (n = 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.
Cappellini
Maria Domenica
MD
Fondazione Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena IRCCS, Universita di Milano, Via F. Sforza 35, 20122 Milan, Italy. maria.cappellini@unimi.it
Cohen
Alan
A
Piga
Antonio
A
Bejaoui
Mohamed
M
Perrotta
Silverio
S
Agaoglu
Leyla
L
Aydinok
Yesim
Y
Kattamis
Antonis
A
Kilinc
Yurdanur
Y
Porter
John
J
Capra
Marcello
M
Galanello
Renzo
R
Fattoum
Slaheddine
S
Drelichman
Guillermo
G
Magnano
Carmelo
C
Verissimo
Monica
M
Athanassiou-Metaxa
Miranda
M
Giardina
Patricia
P
Kourakli-Symeonidis
Alexandra
A
Janka-Schaub
Gritta
G
Coates
Thomas
T
Vermylen
Christiane
C
Olivieri
Nancy
N
Thuret
Isabelle
I
Opitz
Herbert
H
Ressayre-Djaffer
Catherine
C
Marks
Peter
P
Alberti
Daniele
D
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003676:Deferoxamine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012449:Safety; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000378:metabolism
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox