BioWorld International Correspondent

MUNICH, Germany - Biliary cancers, such as gall bladder carcinoma and cholangiocarcinoma, only affect two to four out of 100,000 people, but the diagnosis is often fatal. The tumors usually are detected very late, and patients with biliary cancers have poor prognosis: Median overall survival is between six and eight months following the first diagnosis.

Worse for patients, by the time the cancers are diagnosed they have often spread into the liver, rendering the tumors difficult at best to treat with surgery. Chemotherapy also has proved ineffective.

The sole bright spot seems to be that the tumors are very sensitive to radiation. Wilex AG, of Munich, is starting clinical testing of an antibody that can deliver radioactive iodine-131 specifically to biliary cancer lesions. The company has initiated a Phase I/IIa trial of its candidate, WX-G250RIT, a chimeric monoclonal antibody labeled with I-131 for radio-immune therapy of tumors sensitive to radiation. The company expects that the antibody will accumulate in tumor tissue and deliver radiation directly to the tumor cells, destroying them.

"The compound has already been tested in dose escalation, and it was extremely specific with non-normal tissue," Olaf Wilhelm, CEO of Wilex, told BioWorld International. The radiolabeled compound is an extension of the company's program with WX-G250, an antibody being tested for the treatment of renal cell cancer and has successfully completed Phase I and II clinical trials, with a Phase III trial expected to begin this year.

"We know from preclinical studies that the radiolabeled antibody does not bind to normal tissue," Wilhelm said. "The protein that the antibody binds to is highly overexpressed in the tumors."

The Phase I part of the new trials will examine how the radiolabeled antibody binds to the epithelial cells of the large bile duct and the gall bladder. That will use low radioactive doses suitable for imaging purposes only. The Phase IIa part will evaluate the therapeutic effects of two different radioactive doses, while also examining the compound's safety and tolerance. The trial will be conducted at the University Medical Center Nijmegen in the Netherlands with patients who have gall bladder carcinoma and cholangiocarcinoma that is partly or completely inoperable.

"We pursued the possibility of its applicability for this indication from the very beginning," Wilhelm said. He added that it was a natural outgrowth of the WX-G250 program as a whole. "When you're moving a compound into later stages of testing, you look for other indications," he said. "And when you're a smaller company, you have to focus on getting a product to market relatively quickly. A smaller clinical study helps to make this attractive."

Wilex was founded in 1997 by clinical oncologists from the Technical University of Munich. It has two anticancer platforms, monoclonal antibodies and antimetastatic small molecules, with three products in clinical trials.

Wilhelm believes the G250 program may show results beyond this indication. "In this program, we have the potential to explore other radiosensitive tumors over the course of time."