Assess the safety and efficacy of deferiprone (DFP) in chronically transfused, iron-overloaded patients with sickle cell disease (SCD) or other anemias.

FIRST was a multicenter, 1-year, noninferiority trial of DFP vs deferoxamine (DFO). Patients ≥2 years of age were randomly assigned 2:1 to receive DFP or DFO. Those who completed FIRST could enter FIRST-EXT, a 2-year extension in which all patients received DFP. Thus, the baseline was the start of FIRST for patients randomized to DFP (up to 3 years for the DFP-DFP group), and the start of FIRST-EXT for patients randomized to DFO in FIRST (up to 2 years for the DFO- DFP group). In both studies, efficacy endpoints were yearly changes from baseline in liver iron concentration (LIC), cardiac MRI T2*, and serum ferritin (SF) level. All adverse drug reactions (ADRs) for both studies were recorded.

In FIRST, patients (N = 228) were 46.9% female, mean age was 16.9 (standard deviation [SD] 9.6; range 3–59) years, 84.2% had SCD and 15.8% had other anemias. At 1 year, there were no significant (p > 0.05) differences in change in LIC, cardiac MRI T2*, or SF measures between the DFP and DFO intent-to-treat groups. Common ADRs (≥5% of patients) in the DFP group were abdominal pain, vomiting, pyrexia, increased alanine transaminase, increased aspartate aminotransferase, neutropenia, nausea, and chromaturia; in the DFO group, they were pyrexia and injection site pain. Serious ADRs in the DFP group were neutropenia (2.6%), increased transaminases (1.3%), and agranulocytosis, sickle cell crisis, epididymitis, Propionibacterium infection, bacterial sinusitis (infections not associated with neutropenia), vascular device infection, and migraine (0.7% each); in the DFO group, they were abdominal pain, arthritis, and headache (1.3% each). 134 Patients continued to FIRST-EXT (n = 89 DFP-DFP; n = 45 DFO-DFP): 60.4% were male, mean age was 16.2 (SD 8.6; range 4–47) years, 85.8% had SCD and 14.2% had other anemias. At baseline, all patients had elevated LIC with a mean (SD) of 14.93 (7.61) mg/g dry weight (dw), all had normal cardiac iron with a mean (SD) MRI T2* of 32.69 (17.66) ms, and all but 1 had elevated SF with a mean (SD) of 3894 (2591) μg/L. LIC decreased with mean (SD) reductions of -2.64 (4.64), -3.91 (6.38), and -6.64 (7.72) mg/g dw after 1, 2, and 3 years, respectively (p < 0.01 for all years). Cardiac iron remains in the normal range for all patients. SF levels declined with mean (SD) changes from baseline to years 1, 2, and 3 of -1 (1986), -771 (2171), and -1016 (3617) μg/L, respectively (p < 0.05 for years 2 and 3). No new ADRs (observed in 30.6% of patients) were reported. One patient withdrew due to ADRs of thrombocytopenia and neutropenia, which resolved. Another patient withdrew due to generalized edema and died for reasons unknown 17 days after withdrawal from the study.

DFP effectively controlled iron burden in chronically transfused patients with SCD and other anemias, and it was noninferior to DFO. DFP use was associated with reductions in LIC and SF levels. Cardiac MRI T2* remained normal. DFP was well tolerated in patients who received up to 3 years of treatment, with no new safety concerns. We thank Dr. M Badr, Dr. B Inusa, Dr. AAM Adly, Dr. Y Kilinc, C Fradette, and NT Temin for their contribution to the studies. Sponsored by Chiesi Global Rare Diseases; medical writing support provided by Oxford PharmaGenesis Inc., and funded by Chiesi.