DISCONTINUED: Stages of Development for deferiprone (Ferriprox®)

The drug development process can be thought of as a series of stages, and drugs must successfully pass through each stage to become available to patients. This treatment has been evaluated, and the program has been discontinued. Thus, it is not in the pipeline.

  • An open-label study was conducted in 13 adolescent patients. Subjects were treated for six months with 20-30 mg/kg/d deferiprone. 4 subjects were withdrawn due to side effects, and 9 completed the study. 1 of the 4 subjects who withdrew had agranulocytosis, and the others experienced muscular-skeletal pain, dizziness or Guillain-Barre syndrome which resolved after discontinuation of deferiprone. MRI to assess iron in the dentate nucleus (R2*) and neurologic rating scales were performed at the beginning of the study and at the end.
  • A significant reduction in R2* was observed in 8 of the 9 subjects; the one person who did not show a significant decrease in R2* had an initially low value. It was also observed in the study that there was a modest improvement in neurologic function as measured by the ICARS (8.5 +/- 4.5 pts).
  • Another open-label study was conducted in 20 individuals with FA, ages 8-25, for 11 months to assess the combined therapy of idebenone and deferiprone. Subjects were evaluated with a neurological rating scale (ICARS) and MRI to assess brain iron deposits in the dentate nucleus. All subjects were on a steady dose of idebenone (20mg/kg/d) prior to the start of the study and were maintained on this dose throughout the study. Deferiprone was administered at a dose of 20 mg/kg/day/12 h. One subject was withdrawn after 6 months due to severe neutropenia; another subject had mild neutropenia but was able to complete the study.
  • No significant differences were observed in total ICARS when comparing baseline to the end of the study which was interpreted as a stabilization of neurologic function. Echocardiographic measures showed a significant reduction of left ventricular and intra-ventricular wall thickness. MRI T2* values in the dentate nucleus showed a statistically significant reduction in iron.
  • A double-blind, randomized, placebo-controlled trial was conducted to assess safety, tolerability, and efficacy of multiple doses of deferiprone. Seventy-two patients were randomized to receive 20, 40 or 60 mg/kg/day or placebo. Safety was the primary objective; secondary objectives included standardized neurological assessments (Friedreich Ataxia Rating Scale [FARS], International Cooperative Ataxia Rating Scale [ICARS], 9-Hole Peg Test [9HPT], Timed 25-Foot Walk, Low-Contrast Letter Acuity), general functional status (Activities of Daily Living), and cardiac assessments.
  • Deferiprone was well tolerated at 20mg/kg/day, whereas more adverse events occurred in the 40mg/kg/day than in the placebo group. The 60mg/kg/day dose was discontinued due to worsening of ataxia in 2 patients. One patient on deferiprone 20mg/kg/day experienced reversible neutropenia, but none developed agranulocytosis.
  • Deferiprone-treated patients receiving 20 or 40mg/kg/day showed a decline in the left ventricular mass index, compared to an increase in the placebo-treated patients.
  • Patients receiving 20mg/kg/day of deferiprone had no significant change in FARS, similar to the placebo-treated patients, whereas those receiving 40mg/kg/day had worsening in FARS and ICARS scores. The lack of deterioration in the placebo arm impaired the ability to detect any potential protective effect of deferiprone.