Ferriprox Adverse Drug Reactions in Pooled Clinical Studies and the Literature

12. Ferriprox Adverse Drug Reactions in Pooled Clinical Studies* and the Literature DFP in 2008: >1,100 pts in clinical trials/ compassionate use/active controlled programs. Weekly monitoring, some for > 12 years 21 years of clinical experience Post-marketing exposure(>1999)>20,000 pt-yr A total of 16 deaths were reported during post-marketing experience with deferiprone: 14 deaths were associated with agranulocytosis and 2 deaths - with congestive heart failure secondary to iron overload. Of note, no agranulocytosis-related deaths were reported in any of the ApoPharma-sponsored trials. This could be explained by the protocol requirements for weekly WBC monitoring and discontinuation of deferiprone treatment at the first sign of neutropenia. Three of the fourteen cases of fatal agranulocytosis were reported in the medical literature in patients treated with non-Apotex formulations of deferiprone. The 11 patients who died of Ferriprox?-induced agranulocytosis had received the drug for secondary iron overload associated with thalassemia major (N=5), hemochromatosis (N=2), red cell aplasia including Diamond Blackfan Anemia (N=2), MDS (N=1) and alpha-thalassemia (N=1). The information available to ApoPharma indicates that an adequate monitoring of the neutrophil count and/or an adequate management of the agranulocytosis were not performed in the majority of the fatal cases. Primary cause of death in two out of the eleven patients who developed agranulocytosis was reported as �cerebral hemorrhage� and �pulmonary embolism�. In the rest of the 9 patients the cause of death was reported as �agranulocytosis�. DFP in 2008: >1,100 pts in clinical trials/ compassionate use/active controlled programs. Weekly monitoring, some for > 12 years 21 years of clinical experience Post-marketing exposure(>1999)>20,000 pt-yr A total of 16 deaths were reported during post-marketing experience with deferiprone: 14 deaths were associated with agranulocytosis and 2 deaths - with congestive heart failure secondary to iron overload. Of note, no agranulocytosis-related deaths were reported in any of the ApoPharma-sponsored trials. This could be explained by the protocol requirements for weekly WBC monitoring and discontinuation of deferiprone treatment at the first sign of neutropenia. Three of the fourteen cases of fatal agranulocytosis were reported in the medical literature in patients treated with non-Apotex formulations of deferiprone. The 11 patients who died of Ferriprox?-induced agranulocytosis had received the drug for secondary iron overload associated with thalassemia major (N=5), hemochromatosis (N=2), red cell aplasia including Diamond Blackfan Anemia (N=2), MDS (N=1) and alpha-thalassemia (N=1). The information available to ApoPharma indicates that an adequate monitoring of the neutrophil count and/or an adequate management of the agranulocytosis were not performed in the majority of the fatal cases. Primary cause of death in two out of the eleven patients who developed agranulocytosis was reported as �cerebral hemorrhage� and �pulmonary embolism�. In the rest of the 9 patients the cause of death was reported as �agranulocytosis�.

13. DFP oral solution trial:conclusions FerriproxTM oral solution in young children was not associated with new safety concerns The frequency of adverse reactions was lower than that observed with FerriproxTM tablet formulation in older subjects FerriproxTM oral solution was efficacious in reducing the body iron load in pediatric subjects, as measured by the change in serum ferritin levels FerriproxTM oral solution is a viable alternative for young children requiring chelation therapy.