METHYLGENE TO RESUME DEVELOPMENT OF ITS
HDAC INHIBITOR, MGCD0103 (MOCETINOSTAT)
FDA Lifts Partial Clinical Hold
Montreal, Quebec. September 21, 2009 – MethylGene Inc. (TSX: MYG), today announced that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold placed on MGCD0103, the Company’s proprietary selective histone deacetylase (HDAC) inhibitor for cancer. New patient enrollment in the refractory follicular lymphoma cohort of the Company’s ongoing Phase II clinical trial (Trial 008) is expected to resume as soon as possible.
“We are pleased with the FDA’s action,” said Donald F. Corcoran, President and Chief Executive Officer of MethylGene. “The lifting of the partial clinical hold opens the door to enrolling new patients as well as to further evaluate the development pathways, partnering opportunities and financing options for MGCD0103. The implementation of measures to monitor for pericarditis and pericardial effusion is expected to be relatively straightforward. As previously disclosed at various scientific meetings and in publications, HDAC inhibitors generally, and MGCD0103 in particular, have demonstrated efficacy in a number of tumor types as single agents and in combination therapies. We believe our compound remains a promising opportunity for the treatment of various cancers.”
“Our extensive analysis of the data from 437 patients who were treated with MGCD0103 did not identify a clear correlation between MGCD0103 exposure and pericarditis or pericardial effusion,” said Dr. Jeffrey M. Besterman, Chief Scientific Officer of MethylGene. “In patients treated with MGCD0103, we have seen an incidence of serious adverse events of pericarditis or pericardial effusion of approximately four percent. No pericardial events were fatal and the majority resolved without sequelae. Based on literature and other investigator-driven reviews, the rates of pericardial findings have been reported to vary up to approximately 40 percent for patients with various advanced cancers, who may have received multiple anticancer therapies. The procedures and testing we have in place are relatively simple and non-invasive. We plan to disclose additional data on our findings, which were included in our submission to the FDA, at appropriate scientific venues in the near future.”
The conditions agreed to between MethylGene and the FDA for new patient enrollment in MGCD0103 clinical trials include the exclusion of patients who are diagnosed with cardiac abnormalities prior to starting MGCD0103 therapy (i.e. myocardial infarction, congestive heart failure, and pericardial disease) and patient monitoring by electrocardiogram (EKG) and echocardiography (ECHO) at baseline and while on study. These diagnostic tests are non-invasive and relatively common and inexpensive procedures. The Company’s Complete Response accepted by the FDA included specific guidance for identifying patients at potential risk for, and guidance to manage patients who may develop pericarditis or pericardial effusions. In addition, an independent data safety monitoring board will be implemented with the responsibility of evaluating the safety of MGCD0103 clinical trials. The Company has committed to ongoing data analysis and reporting of any new pericardial events.
“As a lead clinical investigator for MGCD0103 clinical trials, I am pleased to learn that new patients will be able to be enrolled in the Phase II trial of patients with refractory follicular lymphoma,” said Dr. Anas Younes, Professor of Medicine and Director, Clinical Investigation and Translational Research in the Department of Lymphoma/Myeloma, M.D. Anderson Cancer Center. “Data previously reported at the American Society of Hematology and the American Society of Clinical Oncology annual meetings were promising for the compound. The continuation of this trial will help us to further understand the potential role of MGCD0103 in the treatment of lymphomas and other malignancies.”
Previously Disclosed MGCD0103 Clinical Results
MGCD0103 has been evaluated in multiple Phase I and Phase II clinical trials in both solid tumor and hematological cancers and has demonstrated both single-agent and combination activity. Previously reported activity data from several clinical trials are summarized below:
Trial 005: A Phase I/II Study of MGCD0103 and Azacitidine Combination Therapy in Patients with Myelodysplastic Syndrome or Acute Myelogenous Leukemia. Of 52 evaluable patients, 36 percent (19 patients) demonstrated objective responses to the combined treatment. There were eight complete responses (CR), ten complete responses with incomplete peripheral count recovery (CRi), and one partial response (PR)
