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Phase II Clinical Trial of LymphoStat-B Initiated for Treating Systemic Lupus Erythematosus

ROCKVILLE, Md., Sept. 25 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. announced today that it has activated clinical sites and begun to screen patients for randomization and treatment in a Phase 2 clinical trial of LymphoStat-B™ (a human monoclonal antibody to B-lymphocyte stimulator, BLyS™) for the treatment of systemic lupus erythematosus. Dosing of patients for the trial is expected to begin shortly.

Based on the positive results of a Phase 1 clinical trial that were reported in April 2003,(1) Human Genome Sciences has initiated a double-blind, placebo-controlled, multi-center Phase 2 clinical trial designed to evaluate the safety, optimal dosing, and preliminary efficacy of LymphoStat-B. Approximately 300 patients with active systemic lupus erythematosus will be enrolled in the trial and randomized to receive either one of three different doses of LymphoStat-B or placebo. Patients will receive multiple doses of LymphoStat-B or placebo over a 52-week treatment period. Primary endpoints of the trial are safety, optimal dosing, and preliminary efficacy. Efficacy will be measured in the trial according to scores on the SELENA SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) and BILAG (British Isles Lupus Activity Group) disease activity scales. Time to first lupus disease flare also will be recorded.

LymphoStat-B has received a Fast Track Product designation from the U.S. Food and Drug Administration (FDA) for its potential use in treating systemic lupus erythematosus.(1) Human Genome Sciences also plans to initiate a Phase 2 clinical trial of LymphoStat-B in 2003 for the treatment of rheumatoid arthritis.

Results from the previously reported Phase 1 clinical trial demonstrate that LymphoStat-B is well tolerated and biologically active in patients with systemic lupus erythematosus.(1) The Phase 1 trial was a multi-center, double-blind, placebo-controlled, dose-escalation study. The results show 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, the Phase 1 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 Phase 1 results will be presented at the American College of Rheumatology meeting in October.

Ellen Ginzler, M.D., M.P.H., Chief of Rheumatology, SUNY Health Sciences Center at Brooklyn (N.Y.), said, "Lupus is a complex and often devastating chronic illness. Patients with lupus can experience any number of symptoms that can flare unexpectedly, including 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. Unfortunately, only a limited number of treatment options are currently available to these patients. There is a significant need for novel treatment options that can help control disease progression and improve patients' quality of life."

William Stohl, M.D., Ph.D., Professor of Medicine, Division of Rheumatology, University of Southern California, said, "The results of preclinical studies to date, along with the emerging clinical epidemiology data, point to elevated levels of BLyS playing an important contributory role in lupus and in other autoimmune diseases. We look forward to continuing to elucidate the role of BLyS in autoimmune diseases and, hopefully, to realizing the potential of LymphoStat-B in treating autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis."

David C. Stump, M.D., Senior Vice President, Drug Development, said, "We are pleased to advance LymphoStat-B to Phase 2 clinical trials for the treatment of lupus. We have begun to screen patients for treatment under a protocol that will allow us to evaluate LymphoStat-B's safety, optimal dosing, and preliminary efficacy. We were able to initiate this Phase 2 trial rather quickly because of LymphoStat-B's Fast Track status, which allowed us to work closely with the FDA following the completion of the Phase 1 trial, and because of the continued high level of support and enthusiasm for LymphoStat-B in the investigator community. As we have previously indicated, we also plan to initiate a Phase 2 clinical trial of LymphoStat-B in patients with rheumatoid arthritis later this year. We look forward to continuing the clinical development of LymphoStat-B as a potential treatment for lupus and certain other autoimmune diseases such as rheumatoid arthritis."

Craig A. Rosen, Ph.D., President, Research and Development, said, "As a family, autoimmune diseases such as lupus cause immense suffering to millions of patients worldwide. We are delighted to enter LymphoStat-B into Phase 2 clinical development in patients with lupus, and we look forward to our planned initiation of a Phase 2 trial in patients with 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 is a naturally occurring protein discovered by Human Genome Sciences that is required for the development of B-lymphocyte cells 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. In April 2003, LymphoStat-B was given a Fast Track Product designation for the treatment of lupus from the U.S. Food and Drug Administration (FDA).(1) 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.

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.

For more information on LymphoStat-B, see For more information about lupus, rheumatoid arthritis, or autoimmune diseases, visit The Lupus Foundation at, the Arthritis Foundation at, or the National Institute of Arthritis and Musculoskeletal and Skin Diseases at For more information about the FDA's Fast Track Drug Development Programs, see

For additional information on Human Genome Sciences, please visit our web site at

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,, or by calling us at (301) 610-5790, extension 3550.

1. (HGSI Press Release) Results Of Phase 1 Clinical Trial Demonstrate That LymphoStat-B Is Safe And Biologically Active In Patients With Systemic Lupus Erythematosus. April 21, 2003.
2. (HGSI Press Release) Human Genome Sciences Announces the Discovery of a Novel Immune Stimulant. July 8, 1999.
3. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Gross JA, Johnston J, Mudri S, et al. Nature. 2000; 404: 995-999.
4. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Khare S.D., Saarosi I, Xia XZ, et al. Proc Natl Acad Sci USA. 2000; 97: 3370-3375.
5. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. MacKay F., Woodcock SA, Lawton P, et al. J. Exp. Med. 1999; 190: 1697-1710.
6. TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice. Wang H, Marsters SA, Baker T, et al. Nature Immunol. 2001; 2: 632-637.
7. (HGSI Press Release) High Levels of BLyS Implicated in Lupus and Rheumatoid Arthritis Patients. October 30, 2000.
8. Cutting edge: A role for B lymphocyte stimulator in systemic lupus erythematosus. Zhang J, Roschke V, Baker K, Kimberly R, et al. J Immuno. 2001; 166:6-10.
9. Elevated Serum B Lymphocyte Stimulator Levels in Patients with Systemic Immune-Based Rheumatic Diseases. Cheema GS, Roschke V, Hilbert DM and Stohl W. Arthritis & Rheumatism June 2001; 44(6): 1313-1319.
10. A role for BLyS in tissue inflammation? Carter RH. Arthritis & Rheumatism April 2003; 48(4): 882-885.
11. Local production of B lymphocyte stimulator and APRIL in arthritic joints of patients with inflammatory arthritis. Tan S, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, Migone T, Hilbert DM, and Stohl W. Arthritis & Rheumatism April 2003; 48(4): 982-992.
12. Biomarkers in SLE: The Hopkins lupus cohort. Petri M. Lupus Foundation of America Biomarkers for the Assessment of Systemic Lupus Erythematosus Meeting. March 2003.
13. Characterization of a Human Monoclonal Antibody That Antagonizes B- Lymphocyte Stimulator Bioactivities. Les Sekut, Bonnie Sturm, Carol Poortman, Ruth Wager, Chen Zhang, Donara Abramian, Todd Riccobene, Svetlana Sosnovtseva, Cynthia Sung, Viktor Roschke, Kevin P. Baker, David M. Hilbert. American College of Rheumatology 2001 Annual Meeting, Abstract 1377.

Source: Human Genome Sciences, Inc.

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