|MethylGene Initiates MG98 Phase II Trial In Metastatic Renal Cell Cancer|
Wednesday October 6, 9:01 am ET
MONTREAL, QUEBEC--(CCNMatthews - Oct. 6, 2004) -
MG98 / interferon alpha combination investigated as potential first-line therapy
MethylGene Inc. (TSX:MYG - News), a biopharmaceutical company, today announced that it has initiated a randomized, two-step Phase II clinical trial with MG98 in combination with interferon alpha for the treatment of metastatic renal cell cancer.
"Metastatic renal cell cancer is a disease with a very high mortality rate and limited treatment options," said Donald F. Corcoran, President and CEO of MethylGene. "We are hopeful, based on our experience with MG98 as a monotherapy in metastatic renal cell cancer supported by pre-clinical data, that the combination of MG98 with interferon will improve the outcome of patients suffering from this aggressive cancer."
The first step of this trial will involve approximately 30-50 metastatic renal cell cancer patients who have not previously received chemotherapeutic treatment. Patients will be randomly assigned to two dosing schedules which will combine MG98 with interferon alpha. In one schedule, MG98 will be given continuously for seven days, followed by seven days off. In the second schedule, MG98 will be given intermittently as a two-hour infusion, two days per week for three weeks, followed by one week of rest. In both schedules, interferon alpha will be given subcutaneously three times per week. This first step of the trial will evaluate the safety, tolerability, pharmacokinetics, optimal dosing regimen and activity of MG98 combined with interferon alpha.
The second step of the trial will enroll approximately 200 patients at up to 35 sites in North America and Europe. Patients will be randomized to treatment with either a combination of MG98 and interferon alpha or interferon alpha alone. The MG98 dosing schedule for the second step will be selected based on the best results obtained in step one. The primary endpoint of this trial will be median progression-free survival. Secondary endpoints will be tolerability of the combination therapy, one year survival, tumour response and overall survival.
An independent safety monitoring board will be established to review data during the second step of the trial and make recommendations about continued recruitment of patients. Full enrollment of this trial is expected to take between 30 and 36 months.
MG98 is a second-generation antisense oligonucleotide inhibiting the production of the enzyme DNA methyltransferase1 (DNMT1) by targeting its mRNA. If DNMT1 is overexpressed, it may hypermethylate and silence tumour suppressor genes possibly leading to or advancing cancer. Preventing DNMT1 production may allow silenced tumour suppressor genes to be re-activated. In renal cell cancer, it is known that at least six different tumour suppressor genes are methylated or silenced. In addition, interferon appears to have a number of key genes which can be methylated within its biological pathway. In collaboration with the Cleveland Clinic, MethylGene has demonstrated that when renal cancer cell lines resistant to interferon alpha were pre-treated with MG98, they became more sensitive to the induction of cell death by interferon alpha. Those preclinical results, combined with the clinical trial experience with MG98, form the basis for the Phase II combination trial in metastatic renal
About Renal Cell Cancer
Renal cell cancer (also called cancer of the kidney or renal adenocarcinoma) is a disease in which cancer (malignant) cells are found in certain regions of the kidney. Standard treatments of metastatic renal cell carcinoma are limited to high-dose interleukin-2 and interferon alpha with response rates varying between 10-15%. Metastatic renal cell cancer is a disease with a very high mortality rate (82% at two years and 91% by the fifth year after diagnosis in advanced disease). The incidence of renal cell cancer in the United States is 31,900 new cases per year, resulting in 11,900 deaths annually. Since the mid 1970's, kidney cancer has increased at a rate of approximately 2.5% per year in the U.S. In Canada, the incidence is 4,100 new cases per year, resulting in 1,450 deaths annually. The prevalence of the disease is approximately 200,000 patients in the United States.
MethylGene is a biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics in cancer and infectious disease. Two cancer product candidates, MG98, partnered with MGI Pharma in North America and MGCD0103, partnered with Taiho Pharmaceutical for certain Asian countries, are currently in clinical trials. MG98 entered a randomized two-step Phase II combination trial with interferon alpha in metastatic renal cell cancer. MGCD0103 is currently in two Phase I dose-escalation monotherapy trials against solid tumours. In collaboration with Merck, MethylGene is developing small molecule beta-lactamase inhibitors to overcome antibiotic resistance. MethylGene has a portfolio of preclinical programs including inhibitors of kinases and histone deacetylases (HDACs) for both oncology and non-oncology indications. We expect to exploit our HDAC inhibitors in neurodegenerative diseases with EnVivo Pharmaceuticals. Please visit our website at www.methylgene.com.