Celgene Presented Data from Study Evaluating CC-486 in Lower-Risk MDS

Celgene International Sàrl, a subsidiary of Celgene Corporation CELG, today announced that data from a phase I study of oral, epigenetic therapy CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes (MDS) was presented at the 54^th Annual Meeting of the American Society of Hematology in Atlanta, GA. In the study, patients with lower-risk (IPSS Low or INT-1) MDS who were red blood cell transfusion-dependent and/or thrombocytopenic were enrolled and sequentially assigned to receive oral azacitidine 300 mg once daily for either 14 or 21 days of each 28-day cycle. Patients were assessed for safety and hematologic response. At study entry, 40% of patients had received no prior MDS treatment (outside of transfusions), 45% had received erythropoiesis-stimulating agents, and 15% had received white blood cell growth factors. At the time of the analysis, 53 patients had been enrolled. After a median seven treatment cycles for the 14-day treatment arm and five for the 21-day treatment arm, the most frequent grade 3/4 hematologic adverse events in the 14-day arm were anemia (11.5%), thrombocytopenia (11.5%) and neutropenia (7.7%), and in the 21-day arm were neutropenia (18.5%), febrile neutropenia (11.1%) and anemia (7.4%). The most frequent grade 3/4 non-hematologic adverse events were pneumonia (15.4%), vomiting (7.7%), diarrhea (7.7%) and cellulitis (7.7%) in the 14-day arm, and diarrhea (11.1%) and vomiting (7.4%) in the 21-day arm. At data cut-off, 36 patients had discontinued treatment, including eight who discontinued due to adverse events. Three patients in the 21-day arm and two patients in the 14-day arm received reduced doses of oral azacitidine (200 mg) due to adverse events. The overall response rate for patients in the 14-day arm was 42.3% (11/26) and 37.0% (10/27) in the 21-day arm. Additionally, the percentage of patients showing any hematologic improvement was 26.9% (7/26) in the 14-day arm and 29.6% (8/27) in the 21-day arm. The percentage of patients who sustained RBC transfusion independence for 56 days was 53.5% (8/15) in the 14-day arm and 40.0% (6/15) in the 21-day arm. The percentage of patients who sustained RBC transfusion independence for 84 days was 20% (3/15) in the 14-day arm and 33.3% (5/15) in the 21-day arm. Based on these and other early-stage data evaluating CC-486, Celgene plans to initiate two phase III studies (QUAZAR program) evaluating this oral agent in lower-risk MDS and acute myeloid leukemia by the end of 2012. These results are from an investigational study. CC-486 is not approved for any indication.