BioWorld Today Correspondent

Genmab A/S and GlaxoSmithKline plc are starting their Phase III program for ofatumumab in the treatment of rheumatoid arthritis in Europe. U.S. studies are penciled in for next year.

The European leg of the program comprises two studies, each of which will recruit approximately 250 participants. One will enroll patients who have not responded to methotrexate, while the other will recruit patients who have failed treatment with a tumor necrosis factor (TNF)-alpha inhibitor. A 24-week blinded treatment period in each study will be followed by an open-label, 120-week period, during which participants will be offered retreatment if required. Patients in each study will receive two 700-mg doses, plus background methotrexate.

The efficacy of ofatumumab, which binds to the B-cell receptor CD20, will be assessed in terms of its effect on reducing the clinical signs and symptoms of rheumatoid arthritis. The primary endpoint in each study will be a score of ACR20 at 24 weeks, an American College of Rheumatology measure that represents a 20 percent reduction in the number of tender and swollen joints and in several other disease-related parameters.

Peter Sehested, analyst at the Copenhagen, Denmark office of Enskilda Bank, said he was "a bit surprised" that the program was beginning in Europe. "I thought they would go for a U.S. trial right away," he told BioWorld Today.

Lisa Drakeman, CEO of Copenhagen-based Genmab, said that the decision was based on the fact that an earlier approval in Europe was more likely. "It looks like it's possible we might have a different endpoint in Europe," she told BioWorld Today. The company will communicate further information on its U.S. studies shortly, but they will be of a similar size to those in Europe.

Ofatumumab, which London-based GSK in-licensed in a deal valued at up to US$2.1 billion last December, has a similar mode of action to rituximab (Rituxan, Mabthera), which is co-marketed in the U.S. by Cambridge, Mass.-based Biogen Idec and South San Francisco-based Genentech Inc., and in Europe by Basel, Switzerland-based F. Hoffmann-La Roche Ltd. It differs, however, in being a fully human antibody whereas rituximab is a chimeric antibody, a distinction that Genmab thinks could have a difference in chronic treatment settings.

"There are opportunities to penetrate this market particularly as rituximab has become such a large product," Sehested said. "The awareness that rituximab is not an ideal product is becoming more widely known." However, he is not yet convinced that it offers advantages in terms of efficacy. "We haven't been able to find anything that establishes the superiority of the Genmab product as compared with rituximab," he said. "To get this to be a commercial success they have to show something at least as good as rituximab and to show superiority on the safety side."

"If you look at our studies, the delta is pretty big between the placebo patients and the treatment patients," Drakeman said. In a Phase II study in rheumatoid arthritis, an intent-to-treat analysis yielded an ACR20 response rate of 49 percent in the 700-mg treatment group, vs. an ACR response rate of 15 percent in the placebo group.

The same molecule already is undergoing Phase III studies in patients with follicular non-Hodgkin's lymphoma who are refractory to rituximab and in patients with chronic lymphocytic leukemia who have failed fludarabine therapy. "We're hoping to see data from both of those studies next year," Drakeman said.