BioWorld International Correspondent

Genmab A/S plans to move HuMax-CD4, a human monoclonal antibody that binds the D4 T-cell receptor, into a pivotal Phase III clinical trial in patients with cutaneous T-cell lymphoma (CTCL), following its disclosure of positive Phase II data.

"Our hope is to treat the first patients in September," CEO Lisa Drakeman told BioWorld International. That schedule depends on obtaining agreements on the trial design from the FDA, which has designated HuMax-CD4 a fast-track product for treatment of CTCL patients who have failed or cannot tolerate current therapy.

Copenhagen, Denmark-based Genmab aims to recruit CTCL patients with mycosis fungoides (MF), a variant of the condition in which the skin is infiltrated by mushroom-shaped tumors containing malignant T lymphocytes. It constitutes 75 percent of all CTCL cases.

In the Phase II study, 55 percent (10 of 18) of MF patients receiving either 560 mg or 980 mg of drug achieved a partial response, defined as a minimum reduction of 50 percent of the patient's composite assessment score for at least four weeks. "This response data is higher than the response data for the products that are on the market to treat the disease," Drakeman said.

Fourteen of the 18 subjects had early stage disease and received 560 mg of drug. Exactly half attained the primary endpoint. The remaining four subjects had advanced disease and received the higher dosage. Three of them reached the primary endpoint. Just 15 percent (3 of 20) of patients receiving 280 mg of drug achieved the endpoint. In addition, there was a statistically significant difference in CD4 T-cell depletion in the two higher dose groups as compared with the low-dose group. "It's clear from the data that more is better," Drakeman said.

A further nine patients with Sezary syndrome, a rare form of CTCL, also participated in the study but exhibited a lower level of response to treatment at all dose levels. Patients from that category will not be included in the upcoming pivotal study, Genmab said.

Late last year, Genmab reported interim data from the 280-mg group, in which 55 percent of early stage patients and 38 percent of late-stage patients exhibited a partial response. However, that analysis was based on the physician's global assessment not on the composite assessment score. "The one that we're using now is more rigorous because it requires patients to maintain a response for at least four weeks," Drakeman said. (See BioWorld International, Dec. 17, 2003.)

Genmab holds rights to HuMax-CD4 for North and South America only. Its parent company, Medarex Inc., of Princeton, N.J., previously had licensed product rights for the rest of the world to Eisai Co. Ltd., of Tokyo. "We hope we can consolidate the rights," Drakeman said, although she declined to comment on the status of any negotiations that may be under way.

In the meantime, the company is eyeing a 2006 U.S. launch for the product. "We think it's not unreasonable to project that this product could become a $400 million to $500 million product in the U.S.," Drakeman said.