Healthcare Industry News: EnVivo Pharmaceuticals
News Release - June 2, 2008
MethylGene Reports Clinical Data for MGCD0103 at the 44th American Society of Clinical Oncology (ASCO) Annual MeetingCHICAGO, ILLINOIS--(Healthcare Sales & Marketing Network)--Jun 2, 2008 -- MethylGene Inc. (Toronto:MYG.TO ) today announced preliminary data from two ongoing clinical studies with MGCD0103, a novel, isoform-selective histone deacetylase (HDAC) inhibitor, conducted in collaboration with Celgene Corporation and Taiho Pharmaceutical. Results from a Phase II study evaluating MGCD0103 as a single-agent in Hodgkin lymphoma (HL) (Trial 010) were reported in an oral presentation on Sunday, June 1st. A poster presentation describing data from a Phase I/II clinical trial evaluating MGCD0103 in combination with gemcitabine in pancreatic cancer (Trial 006) was reported today. The data from these studies were presented at the 44th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
Isotype-Selective Histone Deacetylase (HDAC) Inhibitor MGCD0103 Demonstrates Clinical Activity and Safety in Patients with Relapsed / Refractory Classical Hodgkin Lymphoma in a Phase II Study, Abstract #8507 (Trial 010)
To date, a total of 38 patients have been enrolled in this ongoing, open-label, Phase II study evaluating the effects of MGCD0103 in relapsed/refractory classical HL. Patients were given MGCD0103 as a single-agent, three times per week for four weeks (one cycle) at an initial starting dose of 110mg, which was reduced to 85mg in more recently enrolled patients. The objectives of this study are to determine the anticancer activity, as well as safety, toxicity and pharmacodynamic markers of MGCD0103 in this patient population. The patients in this study include those who have been heavily pretreated and have progressive disease. Of these patients, all have had prior chemotherapy treatment and 82 percent previously had stem cell transplant therapy. To date, 23 patients are enrolled in the 110mg cohort of whom 20 are evaluable for efficacy. In the 85mg cohort, 15 patients are currently enrolled and 10 are evaluable for efficacy.
Data for the 110mg cohort showed eight patients with objective responses (two complete responses (CR) and six partial responses (PR)), resulting in a 35 percent objective response rate for all enrolled patients in this cohort. Tumor shrinkage was observed in 17 of 20 evaluable patients (85 percent) who had a CT scan. The median duration on study for all enrolled patients was four cycles. The two patients experiencing CRs completed 12 cycles of therapy and came off therapy as per protocol. The median duration of therapy for responders was six cycles. The most common Grade 3 or greater toxicities at this starting dose level were thrombocytopenia (17 percent), pneumonia (17 percent), fatigue (17 percent) and neutropenia (17 percent).
Data presented for 15 enrolled patients in the 85mg cohort showed two patients with partial responses and one patient with stable disease for more than six cycles resulting in an objective response rate of 13 percent and a disease control rate of 20 percent. Tumor shrinkage as measured by CT scan was observed in eight out of ten (80 percent) of patients who had a CT scan. Thrombocytopenia (20 percent), pneumonia (14 percent) and hypotension (14 percent) were the most common Grade 3 or greater toxicities observed in this cohort. The comparison of preliminary safety data at the time of analysis between the 85mg and 110mg cohorts showed a trend toward fewer greater than or equal to Grade 3 drug-related adverse events and fewer drug-related serious adverse events (SAE) at the 85mg starting dose. In addition, we observed a reduction in plasma levels of a potential biomarker, TARC (thymus activation regulated chemokine) in a majority of patients on Day 8 of dosing. Patient enrolment continues at a starting dose of 85mg.
Phase I/II: The Oral Isotype-Selective HDAC Inhibitor MGCD0103 in Combination with Gemcitabine in Patients with Solid Tumors, Abstract #4625 (Trial 006)
Phase I, Solid Tumor Cancers (Including Pancreatic)
In the Phase I portion of the trial, 25 solid tumor patients were enrolled. Twenty were evaluable for efficacy, including ten pancreatic cancer patients. Eligibility requirements include patients for whom gemcitabine is the standard of care, standard therapy failed to produce a response, or no standard therapy exists for their tumor type. In addition, all but three of the enrolled patients had one or more prior treatments including chemotherapy, surgery, radiotherapy, immunotherapy and hormonal therapy. Data for the 20 evaluable patients showed two partial responses and two unconfirmed partial responses for a response rate of 20 percent. In addition, there were seven (35 percent) patients who experience a best response with stable disease. The two confirmed partial responses and three of the stable disease were observed in pancreatic cancer patients.
Phase II, Pancreatic Cancer
The Phase II portion of this trial has enrolled 22 patients to date. Patients eligible for this trial are those with pancreatic cancer who have had no prior treatment with gemcitabine. All patients were administered a starting MGCD0103 dose of 90mg and gemcitabine was dosed as labeled. Results for this pancreatic patient population revealed nine patients (41 percent) experienced stable disease and eight patients are continuing treatment without evidence of disease progression.
In the Phase I portion of the trial, dose levels ranging from 50mg to 110mg were administered three times per week for four weeks (one cycle) and gemcitabine was dosed at a single dose of 1,000mg/m2 weekly for three out of four weeks. The maximum tolerated dose (MTD) was determined to be 90mg and this has been the starting dose administered in the Phase II portion of the trial. The most common Grade 3 or greater toxicities observed in the combined Phase I/II trial (n=42 patients) that are possibly related to MGCD0103 and/or gemcitabine include fatigue (33 percent), thrombocytopenia (24 percent), anemia (21 percent), neutropenia (17 percent), nausea (12 percent) and vomiting (10 percent). Urinary tract toxicities (i.e. cystitis) of Grades 1-3 were also reported in 31 percent of patients enrolled. The assessment of efficacy and response rate for the Phase II portion of the trial is ongoing but appears to have been compromised due to the relatively high rate of early discontinuations. The reasons for the discontinuations reported to date were due to side effects (n=11 patients) and progressive disease (n=3 patients). The reported side effects from MGCD0103 or the combination of MGCD0103 and gemcitabine which caused early discontinuation were: fatigue (6 patients), nausea (2 patients), anemia/mucositis/CHF (1 patient), pericardial effusion (1 patient) and gemcitabine-related toxicity, respiratory failure (1 patient).
"In reviewing the data from this study, we found that in the Phase II portion of the trial, solely in pancreatic cancer patients, the 90mg starting dose of MGCD0103 when given in combination with gemcitabine was not as well tolerated as during the Phase I portion," commented Dr. Robert Martell, Chief Medical Officer of MethylGene Inc. "This resulted in an unexpected level of patients discontinuing the study early. This finding could be related to lower tolerability of the combination in the pancreatic patient population in general, but we also noted that these patients tended to have a poorer performance status than those enrolled in Phase I. As such, we and our partners plan to amend the protocol to use a lower starting dose of MGCD0103 in the combination with gemcitabine. In addition, we may explore an alternative schedule as we enroll additional pancreatic cancer patients throughout 2008."
"It is apparent that MGCD0103 is an active compound and as we continue to evaluate MGCD0103 in various settings, we increase our knowledge about the compound which allows us to better hone in on potential dosing regimens to increase tolerability and durability of response, while achieving an acceptable response rate," said Donald F. Corcoran, President and Chief Executive Officer of MethylGene Inc.
Mr. Corcoran further commented, "looking forward with our partners, we will continue to collect data from our ongoing clinical trials to help guide our decisions regarding future trials and potential registrational studies. The data collected to date demonstrate there is activity with MGCD0103 as a single-agent and in combination with certain approved drugs. It appears that additional scheduling and dose optimization studies will be required prior to embarking on a pivotal single-agent or pivotal combination study. These additional studies could commence once bioequivalency of a formulated product has been established. As previously disclosed, a formulated product is currently in bioequivalency testing as part of our ongoing Trial 012 study. As MGCD0103 clinical trials progress, we will continue to broaden our knowledge about the compound, allowing us to better determine the specific studies that we may want to initiate in collaboration with our partners Celgene and Taiho."
MGCD0103 is an orally-administered, isoform-selective HDAC inhibitor. The compound is currently in one Phase I combination clinical trial with TaxotereŽ for solid tumors, two Phase I/II combination trials with VidazaŽ for hematological malignancies and with GemzarŽ for pancreatic cancer, and five Phase II clinical trials 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 EMEA for the treatment of Hodgkin lymphoma and acute myelogenous leukemia.
MethylGene Inc. (Toronto:MYG.TO ) 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 VidazaŽ, GemzarŽ and TaxotereŽ. 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.
Certain statements contained in this news release, other than statements of fact that are independently verifiable at the date hereof, may constitute forward-looking statements. Such statements, based as they are on the current expectations of management of MethylGene, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond MethylGene's control. These risks and uncertainties could cause future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Such results, performance or achievements include, but are not limited to, the timing and effects of regulatory action; the continuation of collaborations; the results of clinical trials; the timing of enrollment or completion of clinical trials; the success, efficacy or safety of MGCD0103, MGCD265 or MGCD290; the ability to scale up, formulate and manufacture sufficient GMP, clinical or commercialization quantities of MGCD0103, MGCD265 or MGCD290, and the relative success or the lack of success in developing and gaining regulatory approval and/or market acceptance for any compound or new product including MGCD0103, MGCD265 or MGCD290. Such risks include, but are not limited to, the impact of general economic conditions, economic conditions in the pharmaceutical industry, changes in the regulatory environment in the jurisdictions in which MethylGene does business, stock market volatility, fluctuations in costs, expectations with respect to our intellectual property position and our ability to protect our intellectual property and operate our business without infringing upon the intellectual property rights of others, changes in the competitive landscape including changes in the standard of care for the various indications in which MethylGene is involved, and changes to the competitive environment due to consolidation, as well as other risks, which you are urged to read, as described in MethylGene's Annual Information Form for the fiscal year ending December 31, 2007, under the heading 'risk factors,', and all other documents filed by the Company that can be found at www.sedar.com. Consequently, actual future results may differ materially from the anticipated results expressed in the forward-looking statements. The reader should not place undue reliance on the forward-looking statements included in this presentation. These statements speak only as an update on the date they are made and MethylGene is under no obligation to revise such statements as a result of any event, circumstance or otherwise except in accordance with law.
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