Pharmion and MethylGene Report Preliminary MGCD0103 Clinical Data at the 2007 AACR-NCI-EORTC International Conference
- Safety and response data from Phase I/II MGCD0103 combination trial with Gemzar(R) in patients with solid tumors presented -- Preliminary evidence of activity in pancreatic cancer -- Phase II portion of the clinical trial in pancreatic cancer patients has commenced
BOULDER, Colo. and MONTREAL, Oct. 24 -- Pharmion Corporation and MethylGene Inc. today reported preliminary clinical data from the Companies' MGCD0103 Phase I/II combination trial with Gemzar(R) (Trial 006). The data were presented in a poster session at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in San Francisco on October 24th, 2007.
In the poster entitled "Phase I/II: The oral isotype-selective histone deacetylase inhibitor MGCD0103 in combination with gemcitabine in patients with solid tumors," Herbert Hurwitz, M.D., Duke University Medical Center and principal investigator for this trial, described preliminary results for the dose escalation Phase I portion of this trial. The primary objective of the Phase I portion of this trial was to determine the maximum tolerated dose (MTD) of MGCD0103 in combination with Gemzar(R) (gemcitibine) in patients with solid tumors where gemcitibine is considered standard of care or refractory tumors. In the Phase I portion of the study, patients received an oral dose of MGCD0103 three times per week in 28-day cycles at escalating doses ranging from 50mg to 110mg. Gemzar was administered at the standard dose and schedule of 1,000mg/m2 once per week for three weeks followed by one week of rest. Results demonstrated MGCD0103 and Gemzar can be safely administered together at the recommended doses. The MTD was reached and the Companies have initiated the Phase II portion of the study with a recommended dose of 90mg of MGCD0103 in patients with pancreatic cancer. In addition, the pharmacokinetic profile of MGCD0103 appeared not to be altered when administered in combination with Gemzar.
Of the 21 patients enrolled in the study, 13 were evaluable for efficacy at the time of analysis. In summary, of the 13 evaluable patients there was one partial response (PR - RECIST criteria, unidimensional greater than or equal to 30% shrinkage) and eight stable disease (SD). In addition, five of the 13 evaluable patients experienced tumor shrinkage. The PR and a near PR (SD with 29% tumor shrinkage) were observed in pancreatic cancer patients, both of whom remain on study having received six and three cycles of treatment, respectively. Importantly, of the four evaluable patients with pancreatic cancer, there was one PR and three SD, which includes the one near PR.
"MGCD0103 is a very interesting compound as it is the first rationally-designed isotype-selective HDAC inhibitor in clinical development," said Dr. Herbert Hurwitz. "The current study is meant to follow up on strong preclinical data in pancreatic cancer, including synergy with gemcitabine. The Phase I stage of this study shows that the combination of MGCD0103 with gemcitabine is safe with preliminary signs of efficacy in pancreatic cancer. The Phase II stage of the study has been initiated and will better define the potential role of MGCD0103 in patients with pancreatic cancer."
"We are pleased to observe the preliminary tolerability and early signs of clinical activity for the MGCD0103 and Gemzar combination in solid tumor patients and particularly in pancreatic cancer patients. We look forward to expanding our enrollment in this underserved patient population and moving this trial forward during 2008," said Donald F. Corcoran, President and Chief Executive Officer of MethylGene.
"There is tremendous unmet need in pancreatic cancer, and the pre-clinical and clinical data are encouraging," said Dr. Andrew Allen, executive vice president and chief medical officer of Pharmion. "If the signals are sustained, we will move forward with a registrational study in this context, where inhibition of histone deacetylation may enhance the efficacy of gemcitabine. It is possible that the HDAC class-selectivity of MGCD0103, theoretically driving a narrower toxicity profile than pan-HDAC inhibitors, is particularly advantageous in combination with cytotoxic agents."
The combination of MGCD0103 and Gemzar appeared to be well-tolerated in patients with solid tumors which suggest compatibility between the two agents. The 90mg dose is consistent with the single-agent dose for MGCD0103 that is under investigation in Phase II trials for hematologic malignancies. The most common toxicities observed were fatigue, vomiting, anorexia, diarrhea, nausea, headaches and decreased hemoglobin (anemia), all of which were less than or equal to grade 3. In addition, grade 4 hyperkalemia and thrombocytopenia were reported in one patient. Based on determination of the recommended Phase II dose of 90mg and clinical activity, the Phase II portion of the trial has been initiated in gemcitabine-naive patients with metastatic or non-resectable locally-advanced pancreatic cancer. This portion of the study will enroll up to 40 patients.
Pharmion is a leading global oncology company focused on acquiring, developing and commercializing innovative products for the treatment of hematology and oncology patients in the U.S., Europe and additional international markets. Pharmion has a number of products on the market including the world's first approved epigenetic drug, Vidaza(R), a DNA demethylating agent. For additional information about Pharmion, please visit the company's website at http://www.pharmion.com.
MethylGene Inc. is a publicly-traded biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for cancer. The Company's lead product, MGCD0103, is an oral isotype-selective HDAC inhibitor presently in multiple clinical trials for solid tumors and hematological malignancies, including Phase II monotherapy and Phase I/II combination trials with Vidaza(R), Gemzar(R) and Taxotere(R). MGCD265 is an oral kinase inhibitor targeting the c-Met, Tie-2, Ron and VEGF receptor tyrosine kinases. In addition, MethylGene has several preclinical programs: MGCD290 an HDAC inhibitor in combination with azoles for fungal infections; an HDAC program for Huntington's disease; a sirtuins program for cancer; and a beta-lactamase program to overcome antibiotic resistance. MethylGene's development and commercialization partners include Pharmion Corporation, Taiho Pharmaceutical and EnVivo Pharmaceuticals. Please visit our website at http://www.methylgene.com.
Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This release contains forward-looking statements relating to the planned development program for MGCD0103, which express the current beliefs and expectations of management. Such statements are based on current expectations and involve a number of known and unknown risks and uncertainties that could cause Pharmion's future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include, but are not limited to, the potential failure of MGCD0103, to demonstrate safety and efficacy in clinical and non-clinical testing; the ability to complete regulatory submissions and gain regulatory approvals in a timely manner; the ability to initiate and complete trials at the referenced times; the impact of competition from other products under development by Pharmion's competitors; the uncertainty of the regulatory environment and changes in the health policies of various countries; acceptance and demand for new pharmaceutical products and new therapies; uncertainties regarding market acceptance of products newly launched, currently being sold or in development; failure of third-party manufacturers to produce the product volumes required on a timely basis and fluctuations in currency exchange rates. Additional risks and uncertainties relating to Pharmion and its business can be found in the "Risk Factors" section of Pharmion's Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2007, its Annual Report on Form 10-K for the year ended December 31, 2006 and in our other filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made, and Pharmion undertakes no obligation to update publicly or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.