Two patients in the 60-U/kg treatment group Entinostat cost experienced 8 events that were considered to be treatment-related by the investigator; the first patient reported 3 occurrences of itchy throat and 1 occurrence of chest discomfort, and the second patient reported 1 occurrence of gastroenteritis and 3 occurrences of vomiting. Both patients were pre-medicated with H1 blockers and are continuing in the extension study. No patient withdrew from this trial due to an AE. No clinically significant laboratory test abnormalities (hematology,

serum and urinary chemistry) were noted. There were no clinically significant mean changes from baseline observed at the end of the study in any of the laboratory safety parameters. The majority of the vital sign measurements were within normal limits, none of the changes or the measurements outside of the normal limits were clinically significant. Abnormal echocardiography results at month 12 were reported for 2 patients: One patient receiving the 60-U/kg dose had mild tricuspid regurgitation and 1 patient in the 30-U/kg group diagnosed with Type 3c GD (subtype known to have a cardiac involvement) [1], [17] and [18] had a baseline echocardiography that revealed abnormal atrioventricular and mitral valves with

an insufficiency gradient of 30 mm Hg. At study end, the echocardiography results showed pulmonary hypertension with an abnormal tricuspid insufficiency gradient of 74 mm Hg, which was considered a clinically significant deterioration Dabrafenib in vivo but was deemed not related to study treatment. Two patients were found to be IgG positive for anti-taliglucerase-alfa antibodies in at least 1 post-treatment visit; however, this finding did not affect the continued improvement of GD parameters throughout the course of the study. An additional patient was found to be IgG positive at the pretreatment sample and became negative as the trial progressed; this patient also improved clinically as noted above for the other 2 patients. All positive titers were low (< 550). Assay results for neutralizing antibodies (in vitro enzymatic inhibition assay and cell-based neutralizing

assay) were negative for all 3 patients. No apparent association was noted between anti-taliglucerase antibody and safety or efficacy. This study is distinguished among studies of ERT Progesterone for GD in that it is focused exclusively on treatment-naïve pediatric patients. This pediatric study followed the design of the pivotal study in adults regarding dosage, wherein patients were randomized to receive taliglucerase alfa either 30 or 60 U/kg, every other week. However, in this study, the duration was 12 months instead of 9 months and the primary end point was improvement in hemoglobin rather than reduction in spleen volume. At the end of this study, clinically significant improvements were observed in hemoglobin concentration, platelet counts, spleen volume, and liver volume, as well as in GD biomarkers.