Two months after starting a pivotal trial of its B-cell therapy, Humax-CD20, in chronic lymphocytic leukemia, Genmab A/S initiated a second Phase III, this one in patients with follicular non-Hodgkin's lymphoma (NHL) who are refractory to rituximab.

Results from both trials are expected next year, leaving Genmab with two potential pathways for seeking regulatory approval. Marketing applications could be filed in both the U.S. and Europe in 2007, and "the product could be marketed sometime in 2008, if everything goes as planned," said Helle Husted, director of investor relations for the Copenhagen, Denmark-based firm.

The planned NHL study will involve about 162 patients who are refractory to either rituximab in combination with chemotherapy or to rituximab as maintenance treatment. Rituximab is marketed in the U.S. as Rituxan by South San Francisco-based Genentech Inc. and Cambridge, Mass.-based Biogen Idec Inc.

Patients will be randomized into two dose groups to receive an 300-mg infusion of Humax-CD20 (ofatumumab) followed by seven weekly infusions of either 500 mg or 1,000 mg.

The trial's primary endpoint is overall objective clinical response, as measured over a six-month period according to the Cheson criteria for NHL.

Patients will be assessed every three months until month 24.

Humax-CD20, a fully human antibody targeted at the CD20 molecule found in the cell membrane of B cells, is designed to bind to CD20 to deplete the rampant B cells that accumulate in certain types of cancer. Results reported last year from a 40-patient Phase I/II study demonstrated an overall response rate of 43 percent, which included five complete responses, two complete responses unconfirmed and nine partial responses.

Genmab also has finished extensive preclinical work suggesting that its product is "better at binding to [the target] and is more effective in killing B cells" than rituximab, Husted said.

Humax-CD20 also appeared effective regardless of whether CD20 was expressed at high levels or low levels, as opposed to rituximab, which appeared less efficacious when CD20 was found at lower levels.

In May, the company started a Phase III trial to evaluate Humax-CD20 in 100 patients with B-cell CLL who have either failed treatment with fludarabine and alemtuzumab or who failed fludarabine and are intolerant to alemtuzumab. The product won fast-track designation from the FDA in that indication.

Humax-CD20 also is being tested in a Phase II trial in rheumatoid arthritis.

At this time, Genmab holds worldwide rights to Humax-CD20, though "we are talking with a number of potential partners," Husted told BioWorld Today, adding that the company probably would look for a co-development and commercialization agreement.

Along with Humax-CD20, the most advanced antibody in Genmab's pipeline is Humax-CD4 (zanolimumab), which is in pivotal testing in cutaneous T-cell lymphoma. That product was partnered with Geneva, Switzerland-based Serono SA last year for a $70 million up-front payment to Genmab, plus up to an additional $145 million in milestones. Genmab also would be entitled to receive royalties on global product sales.

Shares of Genmab, listed on the Copenhagen Stock Exchange under "GEN," remain unchanged Monday to close at DKK192.

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