|
ROCKVILLE, Md., April 21 /PRNewswire-FirstCall/ --
Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that
results from a Phase 1 clinical trial demonstrate that LymphoStat-B(TM)
(a human monoclonal antibody to B-lymphocyte stimulator, BLyS(TM))
is well tolerated and biologically active in patients with systemic
lupus erythematosus. Human Genome Sciences plans to initiate Phase
2 clinical trials of LymphoStat-B for the treatment of lupus and
for the treatment of rheumatoid arthritis in 2003.
The company also announced that LymphoStat-B has received
a Fast Track Product designation for the treatment of systemic lupus
erythematosus from the U.S. Food and Drug Administration (FDA).
The Fast Track Drug Development Programs of the FDA were established
in response to the Food and Drug Administration Modernization Act
of 1997, which authorized the FDA to take actions to facilitate
the development and expedite the review of new drugs designated
by the FDA as demonstrating the potential to address serious unmet
medical needs. For a new drug to be designated a Fast Track Product,
the condition it is designed to treat must be serious or life-threatening,
and must represent an unmet medical need. In addition, the FDA must
determine that the drug has the potential to address the unmet medical
need and that the development program is designed to evaluate this
potential.
The multi-center, double-blind, placebo-controlled,
dose-escalation Phase 1 clinical trial was designed to determine
the safety and pharmacology of LymphoStat-B in adult patients with
systemic lupus erythematosus who were receiving standard therapies.(1)
Seventy patients were enrolled and randomized in the study. LymphoStat-B
or placebo was administered intravenously at 1 milligram (mg)/kilogram
(kg), 4 mg/kg, 10 mg/kg, or 20 mg/kg. Patients received a placebo,
a single dose of LymphoStat-B, or two doses of LymphoStat-B twenty-one
days apart. Safety was the primary endpoint of the study. Pharmacology
of LymphoStat-B and biological markers of B-cell function also were
evaluated.
Results show that LymphoStat-B is well tolerated with
no clinically significant differences from placebo in adverse events
or laboratory abnormalities. No drug-related serious adverse events
were reported. The half-life of LymphoStat-B was shown to be consistent
with that of other human monoclonal antibodies, and a dose-proportional
pharmacokinetic profile was observed. As expected based on preclinical
research, results show that LymphoStat-B significantly reduces the
levels of circulating B (CD 20) cells, the precursor cells to those
that produce the body's normal and abnormal antibodies. Full results
of the Phase 1 clinical trial will be disclosed in upcoming scientific
meetings and publications as appropriate.
William Stohl, M.D., Ph.D., a lead investigator and
Professor of Medicine, Division of Rheumatology, University of Southern
California, said, "The results of the Phase 1 clinical trial of
LymphoStat-B in patients with systemic lupus erythematosus are encouraging.
The preclinical studies to date and emerging clinical epidemiology
data strongly suggest that elevated levels of BLyS play an important
contributory role in lupus and in other autoimmune diseases. Based
on the preclinical and clinical evidence to date, LymphoStat- B
may be an effective treatment for autoimmune diseases such as systemic
lupus erythematosus and rheumatoid arthritis. I encourage the development
and execution of additional clinical trials to build our understanding
of LymphoStat-B's possible therapeutic role."
David C. Stump, M.D., Senior Vice President, Drug
Development, said, "The positive results from this initial study
of LymphoStat-B provide us with the safety, dosing and biological
activity data needed to support the advancement of LymphoStat-B
into the next phase of clinical trials in adults with autoimmune
diseases. We have met with the FDA and our clinical investigators
to determine the best path forward for evaluating the safety, efficacy
and optimal dosing of LymphoStat-B administered over a longer period
of time and in larger populations of patients with systemic lupus
erythematosus and rheumatoid arthritis. We are particularly gratified
by the FDA's decision to assign Fast Track status to LymphoStat-B
for use in treating systemic lupus erythematosus. The Fast Track
Product designation speaks to the importance of LymphoStat-B's clinical
target and to the seriousness of the unmet medical need."
William A. Haseltine, Ph.D., Chairman and Chief Executive
Officer, said, "LymphoStat-B demonstrates the synergy that can be
achieved by combining genomic and antibody technology. LymphoStat-B
was the first of our human monoclonal antibody drugs to enter clinical
trials. We believe that it also was the first genomics-derived antibody
drug to enter clinical trials. We are pleased that the FDA has designated
LymphoStat-B as a Fast Track Product for use in treating lupus.
We look forward to continuing its rapid development in close cooperation
with the FDA. We plan to advance LymphoStat-B to Phase 2 clinical
trials in both systemic lupus erythematosus and rheumatoid arthritis
later this year."
LymphoStat-B is a human monoclonal antibody that specifically
recognizes and inhibits the biological activity of B-lymphocyte
stimulator, or BLyS. BLyS(TM) is a naturally occurring protein discovered
by Human Genome Sciences that stimulates B-lymphocyte cells to develop
into mature plasma B cells.(2) Plasma B cells produce antibodies,
the body's first line of defense against infection. Laboratory studies
have indicated that higher than normal levels of BLyS may contribute
to the pathogenesis of autoimmune diseases, such as systemic lupus
erythematosus and rheumatoid arthritis.(3), (4), (5), (6) Autoimmune
diseases are diseases in which the body is attacked by its own immune
system.
In lupus, rheumatoid arthritis, and certain other
autoimmune diseases, elevated levels of BLyS are believed to contribute
to the production of autoantibodies -- antibodies that attack and
destroy the body's own healthy tissues. Retrospective and prospective
studies have shown elevated levels of BLyS in the blood of many
patients with systemic lupus erythematosus, and in the blood and
joint fluid of patients with rheumatoid arthritis.(7), (8), (9),
(10), (11) The results of prospective studies also now show a significant
correlation of elevated levels of BLyS with systemic lupus erythematosus
disease activity.(12) LymphoStat-B acts by: (1) binding to BLyS,
(2) inhibiting BLyS's stimulation of B-cell development, and (3)
restoring the potential for autoantibody-producing B cells to undergo
the normal process of apoptosis (programmed cell death). In vitro
and in vivo preclinical studies show that LymphoStat-B can reverse
the immune stimulatory effects of BLyS.(13)
Systemic lupus erythematosus is a serious, life-threatening
disease. Between 200,000 and 500,000 people are diagnosed with systemic
lupus erythematosus each year in the United States alone. The disease
affects between eight and ten times as many women as men. It can
occur at any age, but appears mostly in young people between the
ages of fifteen and forty-five. Symptoms may include extreme fatigue,
painful and swollen joints, unexplained fever, skin rash, and kidney
problems. Lupus can lead to arthritis, kidney failure, heart and
lung inflammation, central nervous system abnormalities, inflammation
of the blood vessels, and blood disorders.
Rheumatoid arthritis is a systemic, chronic autoimmune
disease. Rheumatoid arthritis affects approximately 2.1 million
Americans, mostly women. Rheumatoid arthritis is characterized by
the inflammation of the membrane lining the joint, which is caused
by the body's own immune system attacking healthy joint tissue.
Symptoms typically begin during middle age and may include inflammation
of joints, swelling, difficulty moving, and pain. Daily joint pain
frequently results in limited movement and interferes with a person's
ability to carry out normal activities.
William Freimuth, M.D., Ph. D., Senior Director of
Clinical Research -- Immunology, Rheumatology, and Infectious Disease,
said, "In rheumatoid arthritis, and certain other autoimmune diseases,
elevated levels of BLyS are believed to contribute to the production
of autoantibodies. Autoantibody levels -- especially rheumatoid
factor -- appear to correlate with rheumatoid arthritis disease
severity. We believe that LymphoStat-B inhibits BLyS function, thereby
reducing autoantibody levels, and that it may provide a therapeutic
benefit to these patients. We plan to initiate a Phase 2 clinical
trial of LymphoStat-B before the end of 2003 to explore its potential
for use in treating rheumatoid arthritis. The body of clinical and
preclinical evidence that supports LymphoStat-B's potential role
in the treatment of autoimmune diseases continues to grow, and we
look forward to evaluating this novel drug in both systemic lupus
erythematosus and rheumatoid arthritis patients."
|
Message
Boards
