Dacogen developed by MGI Pharma Inc. is indicated for treatment of patients with myelodysplastic syndromes including previously treated and untreated, de novo and secondary of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System groups.

Dacogen (Decitabine) is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. Dacogen inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Dacogen induced hypomethylation in neoplastic cells may restore normal function to genes that are very critical for the control of cellular differentiation and proliferation. In rapidly dividing cells, the cytotoxicity of Dacogen may also be attributed to the formation of covalent adducts between DNA methyltransferase and Dacogen incorporated into DNA. Non-proliferating cells are comparatively insensitive to Dacogen

Phase 3 Trial

A randomized open-label, multicenter, controlled trial evaluated 170 adult patients with myelodysplastic syndromes meeting French-American-British classification criteria and International Prognostic Scoring System High-Risk, Intermediate-2 and Intermediate-1prognostic scores. Eighty-nine patients were randomized to Dacogen therapy plus supportive care (only 83 received Dacogen), and 81 to Supportive Care alone. Patients with Acute Myeloid Leukemia were not intended to be included. Of the 170 patients included in the study, independent review found that 12 patients had the diagnosis of AML at baseline. Baseline demographics and other patient characteristics in the Intent-to-Treat population were similar between the 2 groups.