A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia

Abstract

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 ␤-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. (Blood. 2006;107:3455-3462)

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

“…Iron determination by MRI is a reproducible, sensitive, and noninvasive method that can reduce the need for liver biopsies to assess liver iron content especially in thrombocytopenic patients. The changes of LIC during the course of our study confirm the high efficacy of deferasirox to mobilize iron deposits from liver tissue [12,32,33]. Given the fact that the primary goal of chelation therapy is to reduce iron deposits, LIC assessment by MRI seems to be the ideal tool to monitor the efficacy of chelation.…”

“…Deferasirox (ICL670, Exjade®) is a once-a-day orally active iron chelator formulated as a dispersible tablet with high iron-binding potency and iron selectivity [12][13][14]. Deferasirox binds iron in a 2:1 ratio before being excreted primarily in the bile [15].…”

“…Deferasirox binds iron in a 2:1 ratio before being excreted primarily in the bile [15]. A series of studies have demonstrated its efficacy and safety in patients with thalassemia major in a daily dose ranging between 20 and 30 mg/kg [12,[16][17][18][19][20][21]. So far, experiences regarding treatment with deferasirox in individuals with diseases other than thalassemia are only limited [20][21][22].…”

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

“…[2][3][4][5][6] The once-daily oral deferasirox dispersible tablet (DT) formulation (Exjade ® ), available since 2005, offered an improved option over parenteral deferoxamine (Desferal ® ), providing greater compliance, patient satisfaction, and health-related quality of life. 7,8 The efficacy and safety of deferasirox DT has been well-defined through an extensive clinical trial program in adult and pediatric patients with a variety of anemias, including thalassemia, myelodysplastic syndromes (MDS), sickle-cell disease, and other rare anemias, [9][10][11][12][13] and has been used in clinical practice worldwide for over a decade. Nonetheless, barriers to optimal patient acceptance of treatment still exist with deferasirox DT, including palatability, the need to take the drug in a fasting state (ie, not being able to take with food), and drug-related side effects, notably gastrointestinal (GI) tolerability.…”

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

“…Yet, unless the aim is to document the superiority of one agent over the other in transfusiondependent MDS patients with anemia, the relevance of such studies may be less evident. 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 The equivalence of deferoxamine and deferasirox has been established in patients with β-thalassemia [46] and sickle cell disease [47], and the pathogenesis of iron overload in these anemias is considered generalizable to other anemias requiring transfusion. The differential benefit of deferasirox is its convenience of once daily oral intake.…”