Results of Phase 1 Clinical Trial Demonstrate That LymphoStat-B(TM) Is Safe and Biologically Active in Patients with Systemic Lupus Erythematosus - Human Genome Sciences to Advance Drug for Treatment of Lupus To Phase 2 Clinical Trials - - Receives F
ROCKVILLE, Md., Apr 21, 2003 /PRNewswire-FirstCall via COMTEX/ -- 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.
(Photo: newscom.com )
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."
For more information on LymphoStat-B, see www.hgsi.com/products/LSB.html. For
more information about lupus, rheumatoid arthritis, or autoimmune diseases,
visit The Lupus Foundation at www.lupus.org, the Arthritis Foundation at
www.arthritis.org, or the National Institute of Arthritis and Musculoskeletal
and Skin Diseases at www.niams.nih.gov. For more information about the FDA's
Fast Track Drug Development Programs, see www.fda.gov.
For additional information on Human Genome Sciences, please visit the web site
at www.hgsi.com.
Health professionals or patients interested in inquiring about LymphoStat- B
trials or any other study involving HGSI products are encouraged to inquire via
the Contact Us section of the Human Genome Sciences web site,
www.hgsi.com/products/request.html, or by calling at 301-610-5790, extension
3550.
Human Genome Sciences is a company with the mission to treat and cure disease by
bringing new gene-based drugs to patients.
HGS, Human Genome Sciences, BLyS and LymphoStat-B are trademarks of Human Genome
Sciences, Inc. |
