Copenhagen, Denmark; July 1 2002 - 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.
1
Inhibition of Keratinocyte Apoptosis by IL-15: A New Parameter in the
Pathogenesis of Posriasis? By Rene Rückert, Khusru Asadullah, Martina
Seifert, Vadim M. Budagian, Ralf Arnold, Claudia Trombotto, Ralf Paus, Silvia
Bulfone-Paus