Genmab HuMax-IL15 Effective Against Psoriasis in Mouse Study
Resume: HuMax-IL15 found to be effective in a mouse model to treat psoriasis. In this study, HuMax-IL15 was superior to cyclosporine A, a standard therapy for psoriasis
COPENHAGEN, Denmark, July 1 /PRNewswire-FirstCall/ -- Genmab A/S (CSE: GEN and Neuer Markt: GE9D) announced today that its human antibody therapeutic HuMax-IL15 effectively treated psoriasis in a mouse disease model. In this study, HuMax-IL15 was superior to cyclosporine A, considered the standard therapy for severe psoriasis.
Psoriasis is characterized by thickening of the skin, immature cells and inflammation which leads to cracked and bleeding skin, pain, disfigurement and sometimes disability. In the Genmab SCID Mice study, HuMax-IL15 treatment reduced thickening of skin equal to or better than cyclosporine A. HuMax-IL15 also had a more marked effect on decreasing the immaturity of the cells, a diagnostic hallmark of psoriasis called parakeratosis that results in the scaliness of psoriatic skin. In addition, HuMax-IL15 more effectively reduced Ki-67, a marker of the excessively proliferating skin cells that cause skin thickening. In a fourth marker, the decrease in the types of cells that are believed to initiate the psoriatic inflammation process, HuMax-IL15 and cyclosporine A worked similarly.
These data are being presented today at the World Congress in Dermatology in Paris, France by Kevin Cooper, MD, Chairman of the Department of Dermatology at University Hospitals of Cleveland & Case Western Reserve University, and a member of Genmab's Scientific Advisory Board. Dr Cooper's presentation is entitled "What's New in Immunodermatology" and will take place at 1500 today, July 1 2002.
HuMax-IL15 is designed to block the activity of an immune system signaling molecule called Interleukin-15 (IL-15) which has been suggested to play a crucial role in the development of psoriasis(1). The data from Genmab's pre- clinical study demonstrates the feasibility of neutralizing IL-15 for the treatment of psoriasis.
HuMax-IL15 is being developed in collaboration with Immunex Corporation and is currently in human clinical trials in a Phase I/II study to treat rheumatoid arthritis. Genmab has completed enrolment in this study which is testing the safety of the antibody at a number of dose levels.
The study
A total of 26 SCID (Severe Combined Immune Deficiency) mice were included in the SCID xenograft psoriasis animal model study. SCID mice are animals which have deactivated immune systems, allowing for psoriatic human skin to be transplanted without rejection. Groups of animals were randomized to receive placebo, HuMax-IL15 or cyclosporine A, an FDA-approved treatment of psoriasis which has been shown to effectively treat psoriasis but at the expense of potential damage to patients' kidneys. Due to its side effects, patients can only receive treatment with cyclosporine A for a limited time, even though they have a chronic disease.
"This study shows HuMax-IL15 has the potential to work on both immune- activation that is critical for driving the tissue response of the disease and the keratinocyte response that is the manifestation of the disease," said Dr Kevin Cooper.
"Psoriasis is a debilitating disease and patients who have limited treatment options can despair of hope," said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab. "With 2% of the world's population affected, new treatments are urgently needed. These animal data are encouraging and I look forward to the results of the ongoing Phase I/II trial and the continued development of HuMax-IL15"
About IL-15
The mechanism of IL-15 in psoriasis has been proposed to be as follows: In the immune system the white blood cells, especially activated macrophages and dendritic cells, are well known potent sources of IL-15 and are present in increased numbers in psoriatic lesions. IL-15 thus produced can induce TNF- alpha, a known critical mediator of psoriasis. In other pre-clinical studies IL-15 has been shown to promote angiogenesis and in the Genmab study the anti IL-15 effect of HuMax-IL15 allowed for a decrease in proliferation of the skin cells in conjunction with a decreased thickening of skin.
In addition, IL-15 may play a role in sustaining the inflammation process by recruiting T-cells that can set off inflammation inducing the proliferation of more T-cells. This then creates a self-sustaining cycle resulting in the production of cytokines that can maintain inflammation and the production of psoriatic lesions.
About Genmab A/S
Genmab A/S is a biotechnology company that creates and develops fully human antibodies for the treatment of life-threatening and debilitating diseases. Genmab has numerous products in development to treat cancer, rheumatoid arthritis and other inflammatory conditions, and intends to assemble a broad portfolio of new therapeutic products arising from research into the human genome. At present, Genmab's commercial opportunities are based upon research conducted at leading international companies, including Roche, Immunex Corporation, Oxford GlycoSciences Ltd., Medarex, Inc., deCODE Genetics, Scancell, Ltd., Sequenom, Inc., Eos Biotechnology Inc., Glaucus Proteomics B.V., Bionomics, Paradigm Therapeutics and ACE BioSciences, as well as in its own laboratories. A broad alliance provides Genmab with access to Medarex Inc.'s array of proprietary technologies, including the UltiMAb(TM) platform for the rapid creation and development of fully human antibodies to virtually any disease target. Genmab is headquartered in Denmark and has operations in Utrecht, The Netherlands and Princeton, New Jersey in the US. For more information about Genmab, visit genmab.com . |
