BioWorld International Correspondent

Shares in Genmab A/S plunged over 60 percent last week on news that it is terminating its lead development program.

Its human monoclonal antibody, HuMax-CD4, failed to show efficacy in a Phase II trial of 155 patients with active rheumatoid arthritis who also were receiving methotrexate.

The Copenhagen, Denmark-based company said there was no significant difference in the primary endpoint of the study at week seven between the American College of Rheumatology (ACR) scores from patients receiving placebo compared to those treated with HuMax-CD4 in combination with methotrexate. Twenty-four percent of patients in the placebo group attained an ACR score of 20. The comparable figures for those in the four active dose groups ranged from 11 percent to 29 percent.

Genmab already has a Phase III trial of HuMax-CD4 under way, in patients with active rheumatoid arthritis who do not respond to treatment with methotrexate and TNF-alpha blocking agents. That program received fast-track status from the FDA in February. (See BioWorld International, Feb. 27, 2002.)

Genmab has halted any further recruitment into the study, but intends to collect data on those who already have been enrolled, in order to investigate the difference between administering HuMax-CD4 in combination with methotrexate vs. treatment with the antibody alone. The company will press ahead with development of HuMax-CD4 for treatment of moderate to severe psoriasis, which is at the Phase IIb stage.

Genmab CEO Lisa Drakeman told BioWorld International that the reasons for the failure were not clear. The company had disclosed promising indications of efficacy in earlier studies. "The only thing we really know that's different is that that these patients were receiving methotrexate," she said.

The news pushes out the company's prospects for launching a product by two to three years, to 2006 or 2007. Investors punished it accordingly. The share price drop was "pretty much in keeping with our model," said Steve Cox, a London-based analyst at Commerzbank AG, of Frankfurt, Germany. "You take HuMax-CD4 out and you go back to a lot of early stage clinical development projects," he said.

Genmab's psoriasis project is now its lead program. "The psoriasis data in the Phase II [study] is much more promising. We have some efficacy and a dose-response curve," Drakeman said. Because of the recent news, Cox is not convinced. "Obviously it raises a lot of questions on CD4 in psoriasis," he said.

The news also has repercussions for European biotechnology as a whole, which, Cox said, lacks companies addressing unmet needs in large clinical indications. "This really was one of the more exciting projects in the European sector," he said.

Although Genmab's development has been set back by this reversal, the company's strategy of building a deep pipeline through multiple collaborations means it has a raft of product opportunities waiting in the wings. "They will continue to bring products through, and it's not as if they've bet the farm on this particular product," Cox said.

Drakeman said Genmab would be open to late-stage in-licensing opportunities if they represented a good fit. But it is not a priority. "We've had one business plan from the beginning. It was to build a broad pipeline to balance risk. We've never changed it and we're not going to change it now," she said. The company now has two projects in the clinic, three in manufacturing development and 15 more at earlier stages of preclinical development.

Genmab's share price fell from DKK92 to close at DKK35.5 when the news broke last week. The sell-off continued, in heavy volumes, during subsequent trading sessions on the Copenhagen Stock Exchange. It closed Monday at DKK31.90.