METHYLGENE, PHARMION BEGIN TRIAL OF HDAC INHIBITOR

MethylGene, along with its partner Pharmion, have initiated a Phase II clinical trial with its isotype-specific histone deacetylase (HDAC) inhibitor product candidate, MGCD0103, in patients with high-risk myelodysplastic syndromes (MDS) or relapsed or refractory acute myelogenous leukemia (AML). Specific patient populations include elderly patients who have previously untreated disease or adult patients who have relapsed or refractory disease.

This open-label, single-agent trial will enroll up to 82 patients and be conducted at leading cancer centers in North America. MGCD0103 will be given orally three times per week for four weeks (one cycle) without interruption at a flat dose of 110 mg. This dose was determined based on safety and efficacy data from the companies' Phase I hematologic malignancy study. Key objectives of the study will be to determine the efficacy of MGCD0103 as a treatment option for these patients. Secondary objectives include determining the safety profile, as well as assessing biomarkers and predictive markers for MGCD0103. The trial is expected to last up to 24 months.

High-risk MDS and AML arise through several cellular events, including mutation and/or epigenetic silencing of tumor suppressor genes. The HDAC-dependent repression of transcription (common in the pathway to development of leukemia) is believed to be an important target for HDAC inhibitors, according to the companies. Therefore, it is hypothesized that specifically inhibiting those HDACs involved in transcription with MGCD0103 may restore normal cell function and inhibit tumor growth with fewer side effects than non-selective HDAC inhibitors.