Montreal, Quebec. June 25, 2008 –MethylGene Inc. (TSX: MYG) announced today the initiation of a Phase II clinical trial (Trial 013) evaluating MGCD0103, an isoform-selective histone deacetylase (HDAC) inhibitor product candidate, in combination with Vidaza(R) (azacitidine for injection), a DNA demethylating agent, in patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).
The study is a three-arm, randomized trial which will enroll up to 180 patients at cancer centers in North America and Europe. Additional information about the clinical trial can be found at www.clinicaltrials.gov.
“We believe this trial can address a key question in the field of epigenetic cancer therapy: Is combination therapy with Vidaza and MGCD0103 superior to either agent alone?” said Dr. Charles Craddock, Professor of Haemato-oncology, University of Birmingham, UK and an investigator for this trial. “Vidaza recently demonstrated a major survival benefit when used to treat patients with high-risk MDS. The Phase I/II data with this combination were also compelling, and we aim to determine definitively whether combination treatment is superior to monotherapy in MDS and AML.”
In December 2007, data was reported from the Phase I/II study investigating the combined use of MGCD0103 and Vidaza in patients with MDS or AML. A 43 percent response rate (n=23) was demonstrated at the 90 mg dose with a median time to response of less than two months. The overall results indicated a 36 percent response rate for patients evaluated at all doses (n=52 evaluable patients) in the study. The most common grade 3 and 4 non-hematological toxicities in the study were fatigue and gastrointestinal in nature (e.g. nausea, vomiting, anorexia, diarrhea, dehydration). The recommended Phase II dose for MGCD0103 was determined to be 90 mg. Vidaza did not affect MGCD0103 pharmacokinetics, nor did co-administration of MGCD0103 impact the pharmacokinetics of Vidaza. A majority of patients exhibited a substantial reduction in peripheral blood mononuclear cell (PBMC) HDAC activity during treatment with the combination.
About MGCD0103
MGCD0103 is an orally-administered, isoform-selective HDAC inhibitor. The compound is currently in multiple clinical trials: a Phase I trial in combination with Taxotere(R) for solid tumors; two Phase I/II trials, the first in combination with Vidaza(R) for hematological malignances and the second with Gemzar(R) for pancreatic cancer; several Phase II monotherapy trials in hematological malignancies and, more recently, a Phase II, three-arm combination trial with Vidaza in hematological malignancies.
MGCD0103 has received orphan drug designation from the U.S. Food and Drug Administration (FDA) and has been designated an orphan medicinal product by the European Medicines Agency (EMEA) for the treatment of Hodgkin lymphoma and AML.
About Myelodysplastic Syndromes (MDS) and Acute Myelogenous Leukemia (AML)
Myelodysplastic syndromes are a serious and life-threatening group of diseases in which the bone marrow does not function normally, resulting in the production of malformed or immature blood cells. The disease begins when a defect occurs in the genetic material (chromosomes) of one of the stem cells in the bone marrow. That stem cell in turn produces cells that carry the defect. The defective cells eventually predominate in the bone marrow and overwhelm healthy blood cells. These defective cells are less able to produce functioning blood cells, which results in low blood cell counts (cytopenias) in the bloodstream.
Without enough healthy blood cells - red, white and platelets - people with MDS are at risk for a variety of symptoms and complications including anemia, weakness, fatigue, infection and bleeding. Bone marrow failure results in death from bleeding and infection in the majority of patients, while transformation from MDS to AML occurs in up to 40 percent of patients. The highest incidence of MDS is in patients over 60 years of age.
According to the Aplastic Anemia and MDS International Foundation, approximately 10,000-30,000 new cases of MDS are diagnosed each year in the United States, although it is difficult to accurately determine the incidence because MDS is not a disease for which the Centers for Disease Control and Prevention (CDC) mandates reporting of cases.
About MethylGene
MethylGene Inc. (TSX: MYG) is a publicly-traded, clinical stage, biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for cancer. The Company’s lead product, MGCD0103, is an oral, isoform-selective HDAC inhibitor presently in multiple clinical trials for solid tumors and hematological malignancies, including Phase II monotherapy and Phase I, Phase I/II and Phase II combination trials with Vidaza(R), Gemzar(R) and Taxotere(R). MGCD265 is an oral, multi-targeted kinase inhibitor targeting the c-Met, Tie-2, Ron and VEGF receptor tyrosine kinases and is in Phase I clinical trials for solid tumor cancers. In addition, MethylGene’s preclinical programs include: MGCD290, an HDAC inhibitor used in combination with azoles for fungal infections, a kinase inhibitor program for ocular diseases, and a sirtuin inhibitor program for cancer. MethylGene’s development and commercialization partners include Celgene Corporation, Taiho Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd. and EnVivo Pharmaceuticals. Please visit our website at www.methylgene.com.
