Vion Pharmaceuticals Inc. decided to move one lead cancer drug into pivotal trials, while expanding the Phase II trials of its other one.

The New Haven, Conn.-based company plans to start pivotal trials of Cloretazine in the first quarter of 2005 in acute myeloid leukemia (AML) patients. While the company previously also had hopes of moving Triapine into pivotal trials next year, it does not intend to do that yet based on preliminary Phase II data in pancreatic and non-small-cell lung cancer patients.

"We're in the final stages of establishing a Phase III trial for Cloretazine," said Howard Johnson, the company's president and chief financial officer. "And with Triapine, we're extending a Phase II trial and we'll continue to await the follow-up on the data from the ongoing trials."

Vion announced its plans after the market closed Thursday. Its stock (NASDAQ:VION) barely moved Friday, dropping 8 cents to close at $3.97.

Vion is finalizing the protocol for the Phase III trial of Cloretazine, a sulfonylhydrazine alkylating agent, in AML. The compound has shown activity in a completed single-agent Phase I trial, a combination Phase I trial with Ara-C, and an ongoing Phase II trial.

The Phase III study will be a randomized comparison of the combination of Cloretazine and Ara-C vs. Ara-C alone in 200 to 300 AML patients in first relapse. Enrollment should take 18 to 24 months, Johnson said.

The ongoing Phase II study was started in March and has accrued more than 50 patients to date at nine centers in the U.S. and Europe. Some patients already have had complete responses.

Cloretazine also is being evaluated in a Phase II trial for patients with primary brain cancers, or gliomas. That study began in May at the Brain Tumor Center of the Duke University Comprehensive Cancer Center. Data should be available in 2005.

Johnson said Vion is open to partnership discussions for Cloretazine.

"Right now we own 100 percent of the marketing rights for Cloretazine," he said. "Our only partnership for Triapine is in China."

Beijing Pason Pharmaceuticals, Vion's partner for China, Taiwan, Macao and Hong Kong, plans to initiate clinical trials of Triapine in China next year.

As for Triapine's recent Phase II data, Vion's CEO Alan Kessman said in a prepared statement that results do not warrant moving into pivotal randomized trials at this time. Progression-free survival and response rates in Phase II trials in pancreatic cancer and non-small-cell lung cancer patients show that a Triapine-gemcitabine combination is not that different from gemcitabine alone.

"Part of the issue here is that the median survival data needs more time to mature," Johnson told BioWorld Today.

Vion is encouraged by preliminary data on median survival in the pancreatic cancer trial and intends to expand the Phase II trial to include an additional 25 to 35 patients. Vion also will look at longer, 24-hour infusions of Triapine.

"From our preclinical work, we believe that the longer infusion could measurably improve the results that we've seen to date," Johnson said.

In the ongoing Phase II trials, Triapine, a ribonucleotide reductase inhibitor, has been administered for four hours intravenously prior to each dose of gemcitabine. Since May 2003, the trials have accrued 60 pancreatic cancer patients and 45 non-small-cell lung cancer patients.

Preliminary data show that patients in the pancreatic cancer trial had a median follow-up for survival of 6.6 months, an objective response rate of 3.3 percent, median progression-free survival of 3.9 months, and median survival of 8.75 months. The patients had no prior chemotherapy for metastatic or unresectable disease.

Patients in the lung cancer trial had received a minimum of one, but not more than two, prior regimens of cytotoxic chemotherapy. The response rate among 38 evaluable patients was 5.3 percent. For all 45 patients, the median follow-up for survival was four months, median progression-free survival was 2.1 months, and the median survival was 6.8 months.

Johnson said it's too early to say when Triapine could move into pivotal trials, like Cloretazine.

"We want to follow the survival data longer," he said, "and we want to begin this longer infusion study and see how that unfolds, as well."

Earlier this year, Vion stopped a single-agent study of Triapine in prostate cancer patients when data from that trial and a Phase II head and neck cancer trial indicated the compound might best be used in a combination therapy. (See BioWorld Today, Feb. 9, 2004.)

Aside from Vion's work with Triapine, the National Cancer Institute is sponsoring clinical trials of the compound that could provide additional registration pathways. Vion also plans to move forward in its plans to evaluate an oral formulation of Triapine.

In the preclinical setting, Vion has been evaluating KS119, a hypoxia-selective compound from the sulfonylhydrazine class; several novel compounds from the heterocyclic hydrazones program; and second-generation TAPET (Tumor Amplified Protein Expression Therapy) vectors, which are modified Salmonella bacteria used to deliver anticancer agents directly to tumors.

Vion plans to file an investigational new drug application for KS119 in 2005. It is working to identify a lead product candidate in its heterocyclic hydrazones program, and it intends to find a partner for the TAPET program.

"KS119 is our most advanced preclinical candidate, so we're clearly focused on it," Johnson said. "With TAPET, due to the fact that we're a small company and have resources that need to be prioritized, we're going to look for a partner."

A final change announced by the company Thursday was the resignation of Mario Sznol, vice president of clinical affairs, who will continue to be a member of the Vion board and will serve as a consultant to the company. In his place, Vion is looking for a chief medical officer with late-stage development and commercialization experience.

As of June 30, Vion had $48.1 million in cash and cash equivalents. In February, the company raised $35.2 million, which was expected to carry it into 2006. (See BioWorld Today, Feb. 11, 2004.)

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