FDA Grants Accelerated Approval to Deferiprone
Friday, October 14, 2011
The US Food and Drug Administration granted accelerated approval to deferiprone (Ferriprox® Tablets, ApoPharma, Inc.), an oral iron chelator for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate.
This approval was based on a prospectively planned analysis of data from previously conducted trials enrolling patients (N = 236) with transfusional iron overload and evidence of inadequate iron removal despite previous treatment with deferoxamine. For these patients, the serum ferritin continued to be greater than 2500 micrograms/liter despite deferoxamine therapy. Approximately 95% of patients had thalassemia syndromes.
Changes in serum ferritin levels from baseline up to one year after starting deferiprone were analyzed. The endpoint of at least 20% decrease in serum ferritin was achieved in 50% of patients (95% CI: 43, 57). The mean serum ferritin prior to treatment was 4416 ± 2288 µg/L and after treatment was 3453 ± 2099 µg/L (mean decrease of 962 ± 1907 µg/L). The majority of patients took a total daily dose of 75 mg/kg/day (25 mg/kg three times daily).
The most common adverse reactions include nausea, vomiting, diarrhea, abdominal pain, neutropenia (which may antedate the development of agranulocytosis), arthralgia and an increase in hepatic transaminases. Torsades de pointes and Henoch-Schonlein purpura have been reported with deferiprone use. The most important serious toxicity associated with deferiprone is agranulocytosis, occurring in 1.7% of patients in the clinical trials. Absolute neutrophil counts must be performed weekly while a patient is receiving deferiprone.
The recommended initial dose of deferiprone is 75 mg/kg/d. The maximum recommended daily dose of deferiprone is 99 mg/kg. Periodic serum ferritin measurements should be used to adjust the dose. If the serum ferritin decreases consistently below 500 mcg/L, temporarily interrupting deferiprone may be necessary.
The efficacy and safety of deferiprone in patients with transfusional iron overload due to myelodysplastic syndrome, sickle cell disorders, and other chronic anemias has not been evaluated.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021825lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).