Gentium's Defibrotide Seen as Active in Multiple MyelomaNEW YORK--(BUSINESS WIRE)--Jun 27, 2007 - Gentium S.p.A. (Nasdaq: GENT) announced the presentation of both clinical and preclinical data that support the safety, activity, synergy and potential mechanism of action of Defibrotide in combination with anticancer therapy in multiple myeloma. Investigators presented both an update from the Company's ongoing Phase I/II clinical trial for patients with refractory or relapsed multiple myeloma with Defibrotide in combination with chemotherapy, as well as a pre-clinical study demonstrating the downregulation of a key regulatory enzyme supporting a novel mechanism of action for Defibrotide in myeloma. Data from both studies was presented at the XI International Myeloma Workshop in Kos, Greece, 25-30 June, 2007.
In the first study, investigators led by Dr Antonio Palumbo of The Italian Multiple Myeloma Study Group, presented data from an ongoing multi-center, phase I/II clinical trial for relapsed or refractory multiple myeloma patients. This study is being conducted in an effort to define the maximum tolerated dose (MTD), safety and potential efficacy of the combination of melphalan, prednisone, thalidomide and Defibrotide (MPTD). Nineteen patients, who received at least three cycles of MPTD were evaluable for toxicity and response. Three escalating dose levels of Defibrotide were evaluated in combination with standard doses of melphalan, prednisone and thalidomide. No other thromboprophylaxis was administered. After a median of 3 cycles, the major response rate, including complete and partial remission was 53% (1CR, 1nCR and 7PR). Responses were seen in all three Defibrotide dose levels. Follow up remains limited and the durability of response appears favorable. MTD was not reached in any cohort. Hematological toxicities (greater than/equal to Grade 3) included neutropenia (47%), thrombocytopenia (10%), anemia (21%), non-hematological toxicities greater than/equal to grade 3 were observed in less than 5% of patients. Importantly only one DVT has been seen to date and no significant peripheral neuropathy has been reported.
In a preclinical study presented by Dr. Cinara Echart, Gentium's Manager of Molecular Biology, at the same meeting, Defibrotide demonstrated the ability to significantly downregulate heparanase gene expression and activity in myeloma cell lines in a dose dependent manner (p less than 0.01). In addition, Defibrotide decreases the myeloma cell invasion through the Matrigel matrix in vitro by 50%. Elevated heparanase expression in humans has been correlated with advanced progression and metastasis of many tumor types, including myeloma. Heparanase acts as a key mechanism for breakdown of extracellular matrix to facilitate tumor invasion and metastasis.
Dr. Antonio Palumbo commented, "The combination of MPTD is promising both in terms of activity and tolerability with the low rate of DVT being especially interesting. Moreover, the preclinical studies with Defibrotide are intriguing, suggesting a wider role for this drug as an orally biovavailable agent in combination with chemotherapy as a potential treatment for multiple myeloma."
Gentium, S.p.A., located in Como, Italy, is a biopharmaceutical company focused on the research, development and manufacture of drugs to treat and prevent a variety of vascular diseases and conditions related to cancer and cancer treatments. Defibrotide, the Company's lead product candidate, is an investigational drug that has been granted a Fast Track Designation by the U.S. FDA to treat Severe VOD in recipients of stem cell transplants, Orphan Drug status by the U.S. FDA to treat and prevent VOD and Orphan Medicinal Product Designation by the European Commission to treat and prevent VOD.
Cautionary Note Regarding Forward-Looking Statements
This press release contains "forward-looking statements." In some cases, you can identify these statements by forward-looking words such as "may," "might," "will," "should," "expect," "plan," "anticipate," "believe," "estimate," "predict," "potential" or "continue," the negative of these terms and other comparable terminology. These statements are not historical facts but instead represent the Company's belief regarding future results, many of which, by their nature, are inherently uncertain and outside the Company's control. It is possible that actual results may differ, possibly materially, from those anticipated in these forward-looking statements. For a discussion of some of the risks and important factors that could affect future results, see the discussion in our Form 20F filed with the Securities and Exchange Commission under the caption "Risk Factors."
Gary Gemignani, 212-332-1666
Chief Financial Officer
Posted: June 2007