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Deferiprone and Deferasirox Equally Effective in Patients With Thalassemia Major: Presented at EHA

By Chris Berrie

AMSTERDAM, THE NETHERLANDS -- June 19, 2006 -- The first oral iron chelator, deferiprone (Ferriprox; Apotex), and the new oral iron chelator, deferasirox (Exjade; Novartis), show similar overall rates of success for the control of body iron load in patients with thalassemia major who are transfusion dependent, according to a comparative study presented here at the 11^th Congress of the European Hematology Association (EHA).

There are now 2 oral iron chelators available on the market, but the 2 have not been compared in head-to-head clinical trials, said investigator Fernando Tricta, MD, vice president of medical affairs, ApoPharm Inc., Toronto, Ontario, Canada.

Dr. Tricta and colleagues carried out an indirect comparison of data from 2 distinct cohorts of patients with thalassemia major who were treated with 1 of the 2 oral iron chelators -- deferiprone and deferasirox. Liver iron concentrations (LIC) and serum ferritin changes were used to estimate the relative efficacies.

This study became possible following the recent release of data for deferasirox, where the LIC analysis was based on the stated primary efficacy endpoints according to patient baseline LIC (2-<7; greater than or equal to 7 to < 10; greater than or equal to 10 mg Fe/g dry weight [dw]). Success was classified as maintenance within 1 to < 7, decrease to within 1 to <7, and decrease of greater than or equal to 3 mg Fe/g dw, respectively, after 1 year of treatment.

Serum ferritin data were extracted as a surrogate marker of efficacy, and expressed as mean changes from baseline to 1 year.

The dose of deferasirox at study entry was based on patient baseline LIC in Fe/g dw (2-3, 5 mg/kg/day; >3-7, 10 mg/kg/day; >7-14, 20 mg/kg/day; >14, 30 mg/kg/day). In contrast, the dose of deferiprone at study entry was 75 to 100 mg/kg/day regardless of patient baseline LIC.

Efficacy calculations also took into account the relatively low reported efficacy of deferasirox at 5 to 10 mg/kg/day, and were based upon the 2 patient baseline LIC groups of 2 to < 7 mg Fe/g dw and greater than or equal to 7 mg Fe/g dw.

For the primary efficacy point, expressed as success rate after 1 year of treatment, these 2 deferasirox groups (n = 276) showed 40% and 59%, respectively, with an overall efficacy of 53%. For deferiprone, while the greater than or equal to 7 mg Fe/g dw group was not significantly different (61%; P = .83), a significantly better success rate was seen for both the 2 to <7 mg Fe/g dw group (81%; P = .0002) and overall (70%; P = .016).

A control for this comparison was provided by deferoxamine (Desferal; Novartis) in both of these studies. Thus, the similar deferoxamine responses of 66% (deferasirox study) and 69% (deferiprone study) supported the view of their comparability.

As the secondary efficacy of absolute change in LIC after 1 year of treatment, the 2 chelators provided similar significant overall reductions in LIC -- deferasirox, 2.4 ± 8.2 mg Fe/g dw (n = 268; P = .001); deferiprone, 1.4 ± 4.0 mg Fe/g dw (n = 60; P = .001). In both cases, there were no significant changes in the LIC < 7 mg Fe/g dw group, with the overall effect arising from the reductions seen for the higher patient baseline group of greater than or equal to 7 mg Fe/g dw, 5.3 ± 8.0 mg Fe/g dw (n = 185; P = .001) and 2.9 ± 4.3 mg Fe/g dw (n = 33; P = .001), respectively.

There were no significant differences between the chelators for the serum ferritin changes over 1 year, according to the 4 patient baseline LIC groups (2-3, >3-7, >7-14, >14 mg Fe/g dw): (in, ± SD) deferasirox, 1189 ± 700 mcg/L (n = 15), 838 ± 817 mcg/L (n = 73), -36 ± 721 mcg/L (n = 80), -926 ± 1416 mcg/L (n = 115); deferiprone, -362 ± 522 mcg/L (n = 6), 73 ± 666 mcg/L (n = 22), 45 ± 606 mcg/L (n = 19), -2329 ± 2867 mcg/L (n = 13).

Dr. Tricta noted that these data arose from distinct cohorts of patients participating in independent clinical trials and that the use of mixed methodologies of liver biopsy and superconducting quantum-interference device biosusceptometer were used within each cohort. He indicated that these results specifically highlight the need for a randomised head-to-head comparison of these 2 iron chelators.

This study was conducted by ApoPharm.


[Presentation title: Chelation Efficacy of Deferiprone and Deferasirox in Patients With Thalassemia Major. Abstract 0006]

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