Long-Term Efficacy and Safety of Deferasirox (Exjade®, ICL670), a Once-Daily Oral Iron Chelator, in Patients with Sickle Cell Disease (SCD).
Authors: Vichinsky Elliott , Coates Thomas D. , Thompson Alexis A. , Mueller Brigitta U. , Lagrone Darlene , Heeney Matthew M. 
Published: October 2019

Abstract
Background: Many patients with SCD require acute or chronic transfusions to manage serious crises or prevent stroke. With age, there is also a risk of progressive renal dysfunction. A 1-year comparative study (109) in iron-overloaded patients with SCD demonstrated similar dose-dependent liver iron concentration (LIC) reductions with once-daily oral deferasirox and deferoxamine (DFO). This analysis presents cumulative long-term efficacy and safety data for patients with SCD receiving deferasirox treatment in a 4-year extension trial.
Methods: In the 1-year core phase, deferasirox and DFO doses were assigned according to baseline LIC. In the extension study, patients either continued treatment with deferasirox (deferasirox cohort) or crossed over from DFO to deferasirox (crossover cohort). Patients with abnormal renal function were excluded. Dose adjustments during the extension phase were based on weight changes, serum ferritin (SF), creatinine, liver function tests and skin rash. Efficacy was determined by monthly SF; safety assessments included all adverse event (AE) monitoring, lab parameters, and ocular, auditory, and physical exams. Data were analyzed with a cut-off of 31 March 2007.
Results: 185 patients entered the extension phase, 132 patients in the deferasirox cohort and 53 patients in the crossover cohort. Patients in the deferasirox cohort have received treatment for a median of 2.1 years. There have been 33 discontinuations (26 deferasirox, 7 crossover patients; 18%) due to: AEs (10), consent withdrawal (12), lost to follow-up (8), unsatisfactory chelation (2), and other (1). Only 1 patient has discontinued in the past 12 months due to pregnancy. No deaths have occurred during this study. In the deferasirox cohort, patients who initially received deferasirox 5/10 mg/kg/d had an increase from baseline in median SF levels at 12 months (+50 ng/mL; baseline 2805 ng/mL), which gradually declined and reached baseline at 24 months (−140 ng/mL) following a dose increase to approximately 20 mg/kg/d (starting at 12 months). SF was either maintained or reduced from baseline in the initial 20 and 30 mg/kg/d dose groups. Patients continue to receive deferasirox treatment in the extension phase trial and, as more data accumulate, the long-term effect of deferasirox at doses of 20–30 mg/kg/day will continue to be assessed. There were no significant changes in markers of liver or renal function in either cohort, and no cases of progressive increases in serum creatinine. The most frequent AEs were vomiting (n=10), nausea (n=23), and diarrhea (n=19); 9 patients experienced skin rash. Most AEs were mild and occurred during the core phase, with a steady decrease in incidence during the extension. No new AEs or safety concerns have been reported thus far in the extension study.
Conclusions: Deferasirox demonstrates dose-dependent efficacy in patients with SCD, with a manageable tolerability profile and no new AEs reported over a median of 2.1 years of treatment.