A Randomized, Controlled Phase II Trial in Sickle Cell Disease Patients with Chronic Iron Overload Demonstrates That the Once-Daily Oral Iron Chelator Deferasirox (Exjade®, ICL670) Is Well Tolerated and Reduces Iron Burden

Repeated blood transfusion to prevent complications places patients with sickle cell disease at risk for morbidity from chronic iron overload. Parenteral chelation with deferoxamine (DFO) is effective at reducing iron overload but patient compliance is generally poor. Deferasirox (DSX) is an investigational iron chelator given orally once-daily. Demonstration of the safety and tolerability of DSX over a 1-year period was the primary objective and efficacy was a secondary objective of the study. Adult and pediatric patients (n=195; n=98 aged Discontinuations were similar in the DSX and DFO groups (11.4 vs 11.1%). The mean ± SD doses of DSX and DFO given were 17.3 ± 6.0 and 36.0 ± 11.4 mg/kg, and transfusional iron intake was 0.21 ± 0.13 and 0.23 ± 0.12 mg/kg/day, respectively. The most common adverse events associated with DSX were generally mild and consisted of nausea, vomiting, diarrhea, abdominal pain and skin rash. Mild non-progressive increases in serum creatinine greater than 33% of baseline and above the upper limit of normal were observed in three patients receiving DSX. One patient on DSX developed an elevated ALT most likely related to drug administration that resolved with its discontinuation. Median mg/kg/day Parameter n Mean ± SD n Mean ± SD DSX DFO DSX DFO LIC change (mg Fe/g dw) 113 −1.3 ± 3.1 54 −0.7 ± 2.6 16.7 32.7 Ferritin change (μg/L) 83 −183 ± 1651 33 −558 ± 951 Ratio iron excretion/intake 105 1.14 ± 0.60 52 1.20 ± 0.78 With both DSX and DFO there was a statistically significant reduction in LIC from baseline (P1 also indicates that DSX was able to induce negative body iron balance. Once-daily oral DSX is well tolerated and appears to have similar efficacy to DFO in reducing iron burden in transfused patients with sickle cell disease.