A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with b-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 b-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 concn. (LIC). The primary endpoint was maintenance or redn. 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 wt. (dw) or higher had significant and similar dose-dependent redns. 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 assocd. with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.