BioWorld International Correspondent

With an FDA special protocol assessment agreement tucked under its belt, Copenhagen, Denmark-based Genmab A/S is moving its lead drug candidate, zanolimumab (HuMax-CD4), into a pivotal Phase III trial in patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL).

The study will assess partial and complete responses during treatment and at an eight-week follow up in patients who are refractory to or intolerant of Targretin (bexarotene) and one other standard therapy.

"We expect to treat patients in April. We're lining them up right now," Genmab CEO Lisa Drakeman told BioWorld International. The trial will take about one year to complete. "We then hope to file for approval before the end of 2006," she said.

CTCLs are indolent cancers, characterized by the invasion of skin tissue by malignant lymphocytes expressing the CD4 receptor, which zanolimumab targets.

The trial will have two components. A change of manufacturer has necessitated an initial, open-label, dose-escalation study, which will characterize the new antibody material in 18 patients. They will be assigned to one of three dosage groups and will receive either 4 mg/kg of body weight, 8 mg/kg or 14 mg/kg. Those correspond to total doses of 280 mg, 560 mg or 980 mg in an average person weighing 70 kg. The second, blinded leg of the trial, which will involve 70 subjects, will assess zanolimumab at the two higher-dose levels. Responses must be at least four weeks in duration. Partial responses will be classified as a minimum 50 percent improvement in the Physicians' Global Assessment score, while complete responses will require a 100 percent improvement.

"The FDA has not given us a target response rate. We need to show objective responses," Drakeman said. In Phase II trials, Genmab obtained partial responses in 55 percent of 18 patients receiving either 560 mg or 980 mg of zanolimumab. Patients also exhibited a lengthy duration of response. "We're very optimistic about this based on the data we have so far," she said.

According to its FDA label, Targretin, a topical treatment marketed by Ligand Pharmaceuticals Inc., of San Diego, achieved a partial response rate in 26 percent of 50 patients.

Genmab holds FDA fast-track designation for zanolimumab in refractory patients. That group represents about half of the total CTCL patient population of 16,000 to 20,000 in the U.S., Drakeman said. Before year-end, the company also plans to launch a pivotal trial in patients who have not failed Targretin or other therapies. A Phase II trial of zanolimumab in non-cutaneous T-cell lymphoma still is at the recruitment stage. No therapy has gained approval for that indication, Drakeman said.

"There's actually as great or a greater medical need there," she said.