-- Vion to Advance Additional Phase I Schedules in Preparation for Phase II Studies and Combinations with other Anticancer Agents --
NEW HAVEN, CT, MARCH 2, 2000 -- VION PHARMACEUTICALS, INC. (NASDAQ NM: VION) today announced it has completed a Phase I single dose study of Triapine®, a potent ribonucleotide reductase inhibitor that blocks a critical step in the synthesis of DNA, thereby preventing the replication of tumor cells. The Phase I study was designed to assess Triapine¹s safety profile and pharmacokinetics when administered intravenously as a two-hour infusion every four weeks. Patients were treated on nine dose levels of Triapine and tolerated the treatment well. Furthermore, at the highest dose level, there were no clinically significant toxicities, and peak serum levels of Triapine exceeded the concentrations required to show activity against tumor cells, as demonstrated in preclinical studies. The trial was conducted at the University of Miami and the Arizona Cancer Research Center.
The favorable safety profile and pharmacokinetics support the continued evaluation of Triapine in schedules optimized for antitumor activity. Preclinical studies have shown that Triapine has the greatest effect on tumors when administered consecutively for several days. Vion is continuing to enroll patients into a second Phase I trial of Triapine administered daily for five days every four weeks and will initiate a Phase I study of 96-hour continuous intravenous infusion in the near future. Subsequent Phase I trials are planned based on preclinical data, generated by the company and its collaborators at Yale University, which showed promising antitumor activity when Triapine was combined with three well-known and highly potent DNA-damaging anticancer agents, etoposide, cisplatinum and cyclophosphamide.
Mario Sznol, M.D., vice president of clinical affairs of Vion Pharmaceuticals, stated, "The extensive preclinical studies conducted by Vion and Yale University to date, combined with these initial clinical results support our strong belief that Triapine has substantial potential to benefit cancer patients. Both the ongoing and planned Phase I studies will allow us to evaluate dose regimens and combinations we believe may be most effective in treating solid tumors and hematologic malignancies."
There are many enzymes involved in DNA synthesis, and those that arrest tumor growth are difficult to selectively manipulate. The reductive conversion of ribonucleotide to deoxyribonucleotides by ribonucleotide reductase is a particularly critical step in the synthesis of DNA, since deoxyribonucleotides are present in extremely low levels in mammalian cells. The development of Triapine is based on the concept that a strong inhibitor of ribonucleotide reductase, which is essential for cellular replication, would be a useful weapon in the therapeutic arsenal against cancer.
Vion is developing Triapine®, a Ribonucleotide Reductase Inhibitor (RRI), as a potential treatment for solid tumors and acute myelogenous leukemia. In preclinical studies, Triapine exhibited significant in vitro and in vivo activity against human ovarian cancer grafted onto mice and in mouse tumors for leukemia and lung cancer. Testing its efficacy on L1210 leukemia in an in vivo murine model, Triapine, administered at low doses, cured 40% of the mice and extended their lives by an average of 2.46 times. On M109 lung carcinoma in an in vivo murine model, Triapine, compared with Taxol, had nearly comparable results.
Vion Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the research, development and commercialization of cancer treatment technologies. Vion's product portfolio consists of TAPET®, a drug delivery platform, and three cancer therapeutics (Promycin®, Triapine and Sulfonyl Hydrazine Prodrugs). TAPET has been shown in preclinical models to effectively deliver anticancer agents while having a minimal toxic effect on healthy normal tissues. TAPET uses genetically altered strains of Salmonella as a bacterial vector, or vehicle, for delivering cancer fighting drugs preferentially to solid tumors. Promycin, which attacks oxygen depleted cancer cells, is currently being evaluated with radiation in a multicenter Phase III clinical trial for the treatment of head and neck cancer. Triapine, which is designed to prevent the replication of tumor cells by blocking a critical step in the synthesis of DNA, is currently being evaluated for its safety in a Phase I clinical trial.
Sulfonyl Hydrazine Prodrugs, compounds that are designed to be converted to unique potent, alkylating agents, are currently being evaluated in preclinical studies. For additional information on Vion and its research and product development programs, visit the company¹s Internet web site at http://www.vionpharm.com.
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