"Daily Oral Iron Chelator ICL670 (Deferasirox) Well Tolerated and Effective in Patients With Transfusional Iron Overload: Presented at EHA"
By Danny Kucharsky
STOCKHOLM, SWEDEN -- June 8, 2005 -- The iron chelator ICL670 is well tolerated and produces a dose-dependent effect on liver iron content in patients with Diamond-Blackfan anaemia (DBA), according to data presented here on June 4[th at the 10th Congress of the European Hematology Association (EHA).
The open-label, noncomparative, multicentre study conducted in 7 countries was designed to evaluate the efficacy and tolerability of ICL670 in a cohort of transfusion-dependent patients with DBA, said lead investigator Gilbert Tchernia, MD, professor and haematologist, Hôpital Kremlin Bicêtre, Le Kremlin Bicêtre, France.
ICL670 (deferasirox) is an orally active iron chelator that can be taken once daily, he said.
The condition is a rare form of anaemia that manifests during infancy and childhood. It results from the failure of the bone marrow to produce red blood cells. According to the Diamond-Blackfan Anemia Foundation, there are more than 350 known cases of DBA in the United States and Canada, and about 400 cases reported in the literature.
Deferoxamine is the current standard iron chelator used for the management of iron overload in patients with DBA. Although effective, this agent is administered subcutaneously for 8 to 12 hours, 5 to 7 times weekly, and is therefore inconvenient, leading to poor patient compliance, Dr. Tchernia said. For this reason, patients with iron overload frequently die from iron-induced cardiac disease, he added.
In Dr. Tchernia's study, subjects were a subgroup from a recently completed multicentre trial in which 184 patients with various transfusion-dependent anaemia received ICL670 for 1 year. Thirty patients with DBA were recruited from that study. They had received at least 8 blood transfusions in the 12 months prior to study entry.
Patients were given 5 mg/kg, 10 mg/kg, 20 mg/kg, or 30 mg/kg daily. At study end (52 weeks), 26 patients remained on their starting dose, 1 had increased the dose, 2 decreased the dose, and 1 patient died of the underlying disease before study end.
Patients received a median of 13.5 blood transfusions during the study.
"The DBA patients enrolled in this study required a substantial number of blood transfusions during the 1-year treatment period," Dr. Tchernia said. Still, ICL670 20 mg/kg/day maintained iron balance and 30 mg/kg/day induced a marked negative iron balance.
The overall success rate of ICL670 in liver iron content was 52% (95% confidence interval [CI] of 33, 71). Overall, liver iron content decreased by a mean of 1.6 mg Fe/g dw over the study duration.
However, while liver iron content decreased in the 20 and 30 mg/kg/day dose groups, it increased in the 5 and 10 mg/kg/day dose groups.
All patients reported at least 1 adverse event, with diarrhoea and vomiting the most common. Eight patients had serious adverse events (including bronchitis, upper respiratory tract infection, and upper abdominal pain) but none were considered related to treatment.
Dr. Tchernia concluded that once-daily oral iron chelation therapy with ICL670 appears to be effective and well tolerated for treatment of iron overload in patients with Diamond-Blackfan anaemia.
The study was supported by Novartis Oncology.
[Presentation title: The Once-Daily Oral Iron Chelator ICL670 is Well-Tolerated and Effective in Treating Transfusional Iron Overload in Diamond-Blackfan Anaemia Patients. Abstract 0475]
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