SAN DIEGO, April 16 /PRNewswire-FirstCall/ -- Metabasis Therapeutics, Inc. announced today that a poster entitled, “A Phase I/II Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of Intravenous (IV) Infusion of MB07133 in Subjects with Unresectable Hepatocellular Carcinoma (HCC)” was presented during the Annual Meeting of the American Association for Cancer Research (AACR). The poster provides data on the safety, tolerability and pharmacokinetics from a dose escalation clinical trial the Company recently completed in 28 patients with unresectable primary liver cancer. In addition, preliminary information regarding evidence of drug activity was provided.
MB07133 is a novel HepDirect(R) prodrug of cytarabine (araC) monophosphate designed to produce the biologically active form of araC, araC triphosphate (araCTP), in the liver tumor where it inhibits cell proliferation and induces cell death. The primary objectives in the study were to determine the maximum tolerated dose, safety profile, pharmacokinetics and anti-tumor activity of MB07133 in patients with unresectable HCC. MB07133 was administered as a continuous IV infusion at escalating doses (300, 600, 1200, 1800, & 2400 mg/m2/day) with three to six patients per cohort during the first seven days of a 28-day cycle; patients were allowed to initiate subsequent cycles until disease progression or unacceptable toxicity occurred.
The results of this first dose escalation trial show that MB07133 at doses up to 2400 mg/m2/day IV infusion is well tolerated in patients with unresectable HCC and that there were no clinically important dose-limiting toxicities associated with the therapy. Few treatment-related hepatic adverse events were observed. A pharmacokinetic analysis was conducted, and the results are consistent with MB07133’s expected liver-targeting mechanism.
In addition to these results, this study also revealed encouraging signs of drug activity, including evidence of tumor shrinkage and disease stabilization. Sixty-eight percent of patients had been previously treated by surgery and/or other non-surgical therapies and had a mean baseline tumor burden of 16.0 centimeters. A total of 92 cycles of treatment have been administered, with 11 patients receiving three or more cycles of treatment and three patients receiving at least 12 cycles. Intra-hepatic tumor reduction was observed in seven patients (25 percent), and increased survival was seen in these patients relative to the other patients in the study.
“We were encouraged by the preliminary results presented at ASCO last year, and by these additional data on safety, tolerability and potential drug activity,” stated Dr. Mark Erion, executive vice president of research and development and chief scientific officer of Metabasis. “MB07133 is a novel drug candidate that uses our HepDirect(R) technology to target the activated form of a well known nucleoside oncolytic, cytarabine, to the liver and liver tumor while decreasing levels in tissues outside the liver. Using this targeting strategy, we hope to enhance anti-tumor activity, while simultaneously reducing potential safety and tolerability concerns. We are encouraged by the results of these studies and the findings indicating that MB07133 treatment results in decreased tumor size or disease stabilization in some patients. With these results, we plan to follow up with studies that could provide valuable safety and efficacy information on MB07133 and its potential as a drug candidate for HCC.”
Dr. Paul Laikind, president and chief executive officer of Metabasis said, “Liver cancer is the fifth most common cancer worldwide and the third deadliest. This fatal disease currently lacks an approved drug therapy or standard of care, and most patients die within four - six months of diagnosis. Although it is still early in the development of MB07133, the results we have seen to date suggest that this could be a potential option for treating HCC patients and therefore warrants further investigation.”
About Metabasis (www.mbasis.com):
Metabasis Therapeutics is a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs to address some of the world’s most widespread and costly chronic diseases. By applying our proprietary technologies and scientific expertise, including unique capabilities for targeting the liver and liver pathways, the Company has established a pipeline that includes preclinical and clinical product candidates targeting metabolic diseases such as diabetes, hyperlipidemia and obesity, as well as liver diseases such as hepatitis and primary liver cancer. Metabasis has developed several proprietary technologies for use in discovering and optimizing drugs, including the NuMimetic(TM) and HepDirect(R) technologies. Metabasis is continuing to identify and develop new product candidates using its proprietary technologies and expertise.
Forward-Looking Statements:
Statements in this press release that are not strictly historical in nature constitute “forward-looking statements.” Such statements include, but are not limited to, references to the clinical trial results, potential success and further development of MB07133. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause Metabasis’ actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. These factors include, but are not limited to, the progress and timing of clinical trials for Metabasis’ product candidates; the fact that positive results from clinical trials does not necessarily mean later clinical trials will succeed; serious adverse side effects of, or serious adverse events related to, Metabasis’ product candidates or proprietary technologies; difficulties or delays in development, testing, obtaining regulatory approval, producing and marketing Metabasis’ product candidates; the potential and progress of preclinical compounds and programs; and other factors discussed in the “Risk Factors” section of Metabasis’ Annual Report on Form 10-K for the year ended December 31, 2006. All forward-looking statements are qualified in their entirety by this cautionary statement. Metabasis is providing this information as of this date of this release and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.
Metabasis Therapeutics, Inc.
CONTACT: Constance Bienfait, Vice President Investor Relations & CorporateCommunications of Metabasis Therapeutics, Inc., +1-858-622-5575
Web site: http://www.mbasis.com/
