GlaxoSmithKlline and Genmab present positive Phase II results with ofatumumab in patients with rheumatoid arthritis (RA)

London, UK, Philadelphia, US and Copenhagen, Denmark

Summary: New data to be presented at the European League Against Rheumatism (EULAR) congress demonstrates the potential benefit of ofatumumab in patients with rheumatoid arthritis.

GlaxoSmithKline (GSK) and Genmab A/S (CSE: GEN) announced today positive primary efficacy data (evaluated at 24 Weeks) to be presented at EULAR 2007, the Annual European Congress of Rheumatology (abstract number: OPO232) from a Phase II study of ofatumumab (HuMax-CD20®) in patients with rheumatoid arthritis (RA). Ofatumumab is being co-developed under a worldwide agreement between GlaxoSmithKline and Genmab.

A total of 225 patients with active RA who have previously failed one or more disease-modifying anti-rheumatic drugs (DMARDs) were enrolled into this double-blind placebo controlled study to evaluate the safety and efficacy of ofatumumab. Patients within the study were randomized into one of four treatment groups (300 mg, 700 mg or 1000 mg ofatumumab or placebo) and assessed based on their AmericanCollegeof Rheumatology (ACR) and EULAR responses at 24 weeks. Continuation of current stable doses of methotrexate and low dose corticosteroids were permitted.

In the intention-to-treat study population, comprising 224 patients, ACR20 was achieved by 46% of all patients receiving ofatumumab, ACR50 achieved by 24% and ACR70 achieved by 6% of ofatumumab patients compared to 15%, 5% and 0% in the placebo group. Evaluated by dose groups, an ACR20 response was obtained by 41% , 49% and 46% of patients receiving 300mg, 700mg and 1000mg of ofatumumab. An ACR50 response was obtained by 19%, 26% and 26% of patients receiving the varying doses of ofatumumab, with 9%, 4% and 6% obtaining an ACR70 response. These scores indicate a 20%, 50% or 70% improvement respectively in the number of swollen and tender joints, as well as improvements in other disease-activity measures.

In the subgroup of patients receiving concomitant stable doses of methotrexate, comprising 178 patients, results across the three dose levels of ofatumumab studied showed that an ACR20 response was obtained by 42% (p=0.006), 56% and 50% (p=0.001) of patients in the 300 mg, 700 mg and 1000 mg dose groups, respectively compared to 16% in the placebo group. An ACR50 response was obtained by 21%, 26% and 26% of patients receiving the varying doses of ofatumumab, with 8%, 2% and 5% obtaining an ACR70 response. The corresponding responses for the placebo group were 7% and 0%.

At 24 weeks, the patients’ immune responses to study medication (ofatumumab or placebo) were also evaluated by testing for the presence of human anti-human antibodies (HAHAs). All patients tested negative at 24 weeks.

Overall, 72% (300 mg ; 700 mg p=0.001; 1000 mg p=0.001) of patients treated with each of the ofatumumab doses experienced at least a moderate (moderate or good) EULAR response compared to 40% of patients receiving placebo at week 24.

The data also showed that ofatumumab appeared well tolerated, with no increased frequency of serious infections. Approximately half of the adverse events occurred on infusion days (51%) with the most frequently reported being mild or moderate (CTC grade 1-2 events), including throat irritation, dyspnoea and rash.

“These results represent another positive milestone in the development of ofatumumab. They will enable us to progress development in the rheumatoid arthritis (RA) indication and help bring this potentially important treatment to patients suffering from this often painful and debilitating condition,” commented Dr. Kathy Rouan, Vice President, Research and Development, GlaxoSmithKline.

“The level of response of patients in the study illustrates the potential of ofatumumab in the treatment of RA and we hope to see similar results in the Phase III study being planned for later this year,” said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab.

These data will be described in an oral presentation by Professor Mikkel Østergaard, Department of Rheumatology, CopenhagenUniversityHospitalat the 2007 Annual European Congress of Rheumatology (EULAR) in Barcelona, Spainon June 16.

ACR Response

The ACR response is a standard assessment used to measure patients’ responses to anti-rheumatic therapies devised by the AmericanCollegeof Rheumatology (ACR). It requires a patient to have a defined percentage reduction in a number of symptoms and measures of their disease. For example:

· At least 20% improvement in the painful joint count and in the swollen joint count; and

· At least 20% improvement in at least three of the following parameters: ESR or APR, physician’s global assessment of disease activity, patient’s global assessment of disease activity, patient’s assessment of pain, and physical disability.

These criteria are known as the ACR20, reflecting the need for a 20% improvement in each parameter, which is considered the clinically relevant cut-off point. A50% or 70% level of reduction (the percentage of reduction of RA symptoms) is represented as ACR50 and ACR70, respectively.

EULAR Response

The EULAR criteria for rheumatoid arthritis use the disease activity scale (DAS)using the 28-joint tender and swollen joint counts, which includes not only change in disease activity but also current disease activity. To be classified as responders, patients should have a significant change in DAS and also low current disease activity. Patients are classified as good, moderate, or non-responders according to both a significant change in the DAS and the level of residual disease activity.