Genmab A/S said Wednesday it is winding down its anti-CD4 development program for rheumatoid arthritis after initial Phase II trial results showed no significant difference in American College of Rheumatology scores for patients who received placebo vs. those treated with HuMax-CD4.
Genmab, based in Copenhagen, Denmark, began a Phase III trial in December in active RA patients who had not responded to other treatments. The company also is stopping enrollment in the Phase III trial. (See BioWorld Today, Dec. 13, 2001.)
Genmab trades on the Copenhagen stock exchange; its shares (CSE:GEN) fell 61.4 percent on Wednesday.
"Our business plan has always been to develop a broad portfolio of products and balance the risk in the company in that way," CEO Lisa Drakeman told BioWorld Today. "Our job is to work on [HuMax-CD4 and HuMax-IL15] in the clinic."
The Phase II trial involved 155 patients with RA who were treated in four active dose groups - 280 mg, 160 mg, 80 mg and 20 mg - plus a placebo arm. Genmab said that there was no significant difference in the ACR scores at the primary endpoint of the study in week seven. Of the HuMax-CD4-treated groups, between 11 percent and 29 percent in the four dose groups achieved an American College Rheumatology score of 20 - the minimum score that indicates efficacy - compared to 24 percent of patients in the placebo group. HuMax-CD4 works by blocking the CD4 receptor on T cells.
Genmab said that while it plans to end recruitment for both the Phase II and Phase III trials of HuMax CD4 in RA, the data gathered thus far would be analyzed. In the Phase III trial, Genmab said it would collect data on patients enrolled thus far and "investigate the difference between using HuMax CD4 in combination therapy with methotrexate vs. the antibody alone." It also will collect safety data on those patients.
Drakeman said she did not know why the antibody failed to be effective in the Phase II trial, which was begun in December 2000 and conducted in Denmark, Sweden, the UK, Iceland and the U.S.
"It's very hard to say," she said. "The preclinical was good, the Phase II was good, but we've seen a lot of products not work this year. The only difference between this study and previous studies was that [patients] were able to take methotrexate."
Genmab had planned to file for FDA approval of HuMax CD4 in RA in early 2004, and the agency had granted HuMax-CD4 fast-track status. (See BioWorld Today, June 7, 2002.)
Genmab will continue with its Phase IIb development plans using HuMax-CD4 in patients with moderate to severe psoriasis, the company said. Genmab was granted North American rights to HuMax-CD4 by Princeton, N.J.-based Medarex Inc. HuMax-CD4 was created using Medarex's UltiMAb Human Antibody Development System. Medarex owns about 33 percent of Genmab's stock. Genmab was established in February 1999 by a group of Danish investors and Medarex. (See BioWorld Today, Dec. 13, 2001.)
To emphasize the company's pipeline, Drakeman noted that Genmab has seen "much more encouraging" results to date from its second clinical product, HuMax-IL15. That antibody has completed a Phase I trial and is set to begin a Phase II trial in rheumatoid arthritis before the end of the year, Drakeman said.
Genmab also has other ongoing activities. For example, in January, the company entered an agreement with Medarex and Oxford GlycoSciences plc, of Oxford, UK, that combined targets discovered by OGS's proteomics platform with the capabilities of Medarex and Genmab. (See BioWorld Today, Jan. 10, 2002.)
In June, F. Hoffmann-La Roche Ltd., of Basel, Switzerland, said it would invest $20 million in Genmab as part of an agreement to expand a year-old deal between the companies that ultimately could be worth $100 million. The program is being coordinated by Roche's proteomics group and focuses on developing biologics. (See BioWorld Today, June 7, 2002.)