BioWorld International Correspondent

MUNICH, Germany - The long wait for products from German biotechnology companies came closer to ending this week, as Wilex AG, an oncology specialist in Munich, began the pivotal Phase III trial of its lead compound, Rencarex.

The study is a global, multicenter, randomized evaluation of the antibody's effectiveness as an adjuvant therapy for patients with clear-cell renal-cell carcinoma (RCC). Wilex has called the study ARISER (Adjuvant Rencarex Immunotherapy Trial to Study Efficacy in Nonmetastasized Renal-Cell Carcinoma).

"We had excellent results from out three Phase II trials," Olaf Wilhelm, CEO of Wilex, told BioWorld International. "The most important of these was with the antibody as a monotherapy. The median survival time for our patients was 16 months; in comparable patient groups receiving systemic standard treatments it is about 10 months. Two-year survival is usually 16 percent, and we reached 39 percent."

"The approach to our Phase III trial is also part of an overall paradigm shift in oncology," Wilhelm added. "The earlier the stage at which you can treat a patient, the higher are the chances to actually control the disease and turn it into a chronic disease."

The study will follow a segment of people with renal-cell carcinoma: patients who are disease-free following the surgical removal of a kidney, but who have a high risk of developing metastatic RCC. Wilex designed the trial to detect significant differences in disease-free survival among patients receiving treatment and those receiving a placebo. The company also will conduct long-term follow-up to determine overall survival rates. Slightly more than 600 patients will be enrolled, from more than 50 sites in Europe and the U.S.

"We're looking at a specific subgroup that has no visible lesions after surgery, but still have a high rate of relapse," Wilhelm said. Treatment will be on an out-patient basis, with patients receiving a weekly dose. "We received approval for this approach from the regulatory authorities because the drug has no side effects," he added. "The double-blind placebo-controlled study will give us very robust data."

Wilex plans to finish enrollment in 20 months, and the study's primary endpoint will be time to progression.

"This is clearly defined," Wilhelm said, "because we will monitor therapeutic outcome every three months. The trial is set up with the calculation that we will have a 50 percent relapse rate within 24 months. The analysis, however, is event-driven, so that if you have a certain number of relapses, then you could see statistically significant results. The trial could also wind up shorter than we plan."

Rencarex is a highly specific IgG1 monoclonal antibody that binds to a cell-surface antigen, the MN-antigen, also called G250-antigen or CA IX, which is found on 95 percent of clear RCC cells but not on normal tissue. The antibody originally was developed at the University of Leiden in the Netherlands by Sven Warnaar, who was Wilex's chief scientific officer from 1999 until his retirement in 2003. The company has received orphan drug status from both the FDA and EMEA for Rencarex for use against RCC.

Wilex also is in a position to let the science, rather than the financing, drive both trial design and corporate development. "There's no shortcut to good data," said Wilhelm. "In the non-metastatic setting, we are heading for a $400 million peak-sale market; sophisticated investors like to support the best strategy going forward.

"Obviously, there are some limits," Wilhelm added. "If you were in a pure adjuvant setting, the trial could never be finished. So you aim for a specific subgroup, where you can get results within a reasonable time frame."

In addition to Rencarex, the company has a UPA inhibitor in clinical trials, two compounds in preclinical testing and a number of additional research programs. Wilex was founded in 1997 and has raised €37.5 million in private investment.

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