BioWorld International Correspondent

Genmab moved HuMAX-CD20 (ofatumumab) into a Phase III trial in chronic lymphocytic leukemia (CLL), the first of three pivotal studies it plans to commence this year.

HuMAX-CD20, a monoclonal antibody targeting the B-cell CD20 antigen, will be evaluated in about 100 CLL patients who either have failed on fludarabine and Campath (alemtuzumab) therapy, or who have failed on fludarabine and are resistant to or otherwise ineligible to receive alemtuzumab.

Participants will receive eight weekly infusions, followed by four monthly infusions. The first dose will consist of 300 mg of antibody, whereas all subsequent doses will comprise 2,000 mg of the drug. The primary endpoint of the study will be an objective response to therapy during the 24-week period from the start of treatment. Responses, Genmab said, will be assessed by an independent endpoints review committee using the National Cancer Institute Working Group guidelines.

For comparison purposes, the Copenhagen, Denmark-based company is looking to results obtained in a pivotal trial in the same indication with Campath, now marketed by Cambridge, Mass.-based Genzyme. "Of course we've had several discussions with the FDA about this, and it's pretty clear that they would expect us to at least achieve a similar amount of responses as was achieved with the Campath fast-track study," Genmab Chief Operating Officer Claus Møller said on a conference call. "They achieved 33 percent complete and partial responses in their study over a duration of four to six months."

That figure represents the bar for HuMAX-CD20.

"Personally, I hope we can do it even better, but we'll have to wait and see," Møller said. In a previous Phase I/II trial, HuMAX-CD20 achieved an objective response rate in 46 percent of patients that was of at least eight weeks duration.

The large quantity of antibody required for a complete course of therapy has raised questions about Genmab's pricing intentions in CLL.

"It could be very costly for the CLL patients to have 22 grams of therapy, and when the time comes to think about pricing, we'll take that into account," said Genmab CEO Lisa Drakeman. "Some companies have strategies where there's a maximum price that a patient would pay in a year, for example, for therapy. So I think we'll look for a wide variety of alternatives at the time. Our first goal is to make this available. Our next goal will be to do everything we can so that the patients who need the drug can get access to it."

The company aims to have the data available from the study during 2007. It plans to move HuMAX-CD20 into a Phase III trial in non-Hodgkin's lymphoma this year. The same molecule also is undergoing a Phase II trial in rheumatoid arthritis. It also will commence a pivotal study of HuMAX-EGFr in refractory head and neck cancer this year.

HuMAX-CD4 (zanolimumab) entered a Phase III trial in mycosis fungoides, the most common form of cutaneous T-cell lymphoma, last year. (See BioWorld International, April 27, 2005.)

"I would definitely say HuMAX-CD20 is one of the most promising compounds for Genmab and also one of their most important compounds because it is not partnered right now," Carsten Lønborg Madsen, analyst at Danske Equities in Copenhagen, told BioWorld International. "Of course, Genmab has a lot of money in its chest, but they've always stated they would look for a partner." Given the current vogue for acquiring biotechnology companies with a pipeline of therapeutic antibodies, the company could become an acquisition target, although the firm has itself ruled this out, Madsen said.

Despite the prospect of a lucrative near-term licensing deal with a large pharmaceutical company, Madsen has a sell rating on the stock, as he said there is little room for improvement in its share price at present. "Of course there are lots of possibilities for Genmab. I still think it's an expensive biotech company to own," he said. The company is valued at about DKK7.2 billion (US$1.2 billion) at present. It reported DKK2 billion in cash on March 31.