Press Release: GlaxoSmithKline and Genmab Present Positive Phase II Results With ofatumumab in Patients With RA
GlaxoSmithKline and Genmab Present Positive Phase II Results With ofatumumab in Patients With Rheumatoid Arthritis LONDON, England; PHILADELPHIA, Pennsylvania and COPENHAGEN, Denmark, June 15 -- GlaxoSmithKline (GSK) and Genmab A/S 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-CD20Â®) 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 American College of 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% (p=0.002), 49% (p<0.001) and 46% (p<0.001) of patients receiving 300 mg, 700 mg and 1000 mg 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% (p<0.001) 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 p<0.001; 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 0stergaard, Department of Rheumatology, Copenhagen University Hospital at the 2007 Annual European Congress of Rheumatology (EULAR) in Barcelona, Spain on June 16. ACR Response The ACR response is a standard assessment used to measure patients' responses to anti-rheumatic therapies devised by the American College of 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. A 50% 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. About GlaxoSmithKline GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline on the World Wide Web at www.gsk.com. About Genmab A/S Genmab A/S is a biotechnology company that creates and develops human antibodies for the treatment of life-threatening and debilitating diseases. Genmab has numerous products in development to treat cancer, infectious disease, rheumatoid arthritis and other inflammatory conditions, and intends to continue assembling a broad portfolio of new therapeutic products. In addition, Genmab has developed UniBody(TM), a new proprietary technology that creates a stable, smaller antibody format. Genmab has operations in Europe and the US. For more information about Genmab, visit www.genmab.com. This press release contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with product discovery and development, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. Genmab is not under an obligation to up-date statements regarding the future following the publication of this release; nor to confirm such statements in relation to actual results, unless this is required by law. 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