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Patient Enrollment Completed for Phase 2 Trial of LymphoStat-B for Systemic Lupus Erythematosus

ROCKVILLE, Md., July 29 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. announced today that it has completed the enrollment, randomization and initiation of dosing of patients in a Phase 2 clinical trial of LymphoStat-B™ (human monoclonal antibody to B-lymphocyte stimulator, BLyS™) for the treatment of systemic lupus erythematosus.

The double-blind, placebo-controlled, multi-center Phase 2 clinical trial is designed to evaluate the safety, optimal dosing, and efficacy of LymphoStat-B. A total of 449 patients with active systemic lupus erythematosus have been enrolled in the trial and randomized to receive one of three different doses of either LymphoStat-B or placebo over a 52-week treatment period, in addition to standard-of-care therapy. 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) SLE disease activity scales. Time to first lupus disease flare also will be measured.

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) and has been selected for participation in FDA's Continuous Marketing Application Pilot 2 Program(2). Human Genome Sciences also has completed the enrollment, randomization and initiation of dosing of a Phase 2 clinical trial of LymphoStat-B for the treatment of rheumatoid arthritis (the subject of a separate press release distributed today)(3).

Results from a Phase 1 clinical trial presented at the American College of Rheumatology annual meeting in October 2003 demonstrate that LymphoStat-B is well tolerated and biologically active in patients with systemic lupus erythematosus(4). 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.

Daniel J. Wallace, M.D., Clinical Professor of Medicine, David Geffen School of Medicine, UCLA (based at Cedars-Sinai Medical Center, Los Angeles), said, "Lupus is a complex and often devastating chronic illness that can lead to arthritis, kidney failure, heart and lung inflammation, central nervous system abnormalities, inflammation of the blood vessels, and blood disorders. It can occur at any age, but appears mostly in young women between the ages of fifteen and forty-five. Only a limited number of treatment options are currently available to patients with lupus, and there is a significant need for new treatments that can help control disease progression and improve the quality of life. Laboratory studies have indicated that higher than normal levels of BLyS may contribute to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus(5,6,7,8). We look forward to continuing to elucidate the potential use of LymphoStat-B for the treatment of systemic lupus erythematosus."

Sandra C. Raymond, President and Chief Executive Officer, Lupus Foundation of America, said, "It has been nearly forty years since a new drug has been approved for lupus. We need safer, more effective therapies for this life- threatening disease. The LymphoStat-B Phase 2 clinical trial is one of the largest ever conducted in lupus patients, and we will be following it with great interest, particularly since LymphoStat-B is intended to treat the underlying disease of lupus, rather than treating an individual symptom."

David C. Stump, M.D., Executive Vice President, Drug Development, said, "We are pleased to have completed the enrollment of our Phase 2 clinical trial of LymphoStat-B for the treatment of systemic lupus erythematosus. The continued high level of support and enthusiasm for LymphoStat-B in the investigator and patient advocacy community made rapid progress possible. In addition, LymphoStat-B's Fast Track status and its selection for the FDA's Continuous Marketing Application Pilot 2 Program allowed us to work closely with the FDA following completion of the Phase 1 trial. The Phase 2 study will evaluate LymphoStat-B's safety, optimal dosing, and efficacy. We expect that results will be available in the Fall of 2005. Given the number of patients enrolled and the study's greater than eighty percent statistical power to detect a clinically meaningful benefit, we are confident that the results will be very informative for a decision on LymphoStat-B's further development. We look forward to that important milestone for the clinical development of LymphoStat-B as a potential treatment for lupus and certain other autoimmune diseases."

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(9). Plasma B cells produce antibodies, the body's first line of defense against infection. 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. Preclinical and clinical studies demonstrate that B-cell antagonists can reduce autoantibody levels and help autoimmune disease activity(8,17,18).

Retrospective and prospective studies have found elevated levels of BLyS in the blood of many patients with systemic lupus erythematosus(10,11,12,13,14). The results of prospective studies now show a significant correlation of elevated levels of BLyS with systemic lupus erythematosus disease activity(15,16). 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)(19).

LymphoStat-B was created through a collaboration between Human Genome Sciences and Cambridge Antibody Technology. Human Genome Sciences holds exclusive commercial rights to the drug.

Systemic lupus erythematosus is a serious, life-threatening disease. Between 200,000 and 500,000 people are diagnosed with systemic lupus erythematosus 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.

For more information on LymphoStat-B, see https://www.gsk.com/. For more information about lupus, rheumatoid arthritis, or autoimmune diseases, visit The Lupus Foundation at https://www.lupus.org/, the Arthritis Foundation at https://www.arthritis.org/, or the National Institute of Arthritis and Musculoskeletal and Skin Diseases at https://www.niams.nih.gov/. For more information about the FDA's Fast Track Drug Development Programs, see https://www.fda.gov/.

For additional information on Human Genome Sciences, please visit our web site at https://www.gsk.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, https://www.gsk.com/, or by calling us 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.

Footnotes:
(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 Selection of LymphoStat-B for Participation in FDA's Continuous Marketing Application Pilot 2 Program. March 4, 2004.
(3) (HGSI Press Release) Human Genome Sciences Completes Patient Enrollment in a Phase 2 Clinical Trial of LymphoStat-B for the Treatment of Rheumatoid Arthritis. July 29, 2004.
(4) (HGSI Press Release) Human Genome Sciences Reports Results of Phase 1 Clinical Trial of LymphoStat-B in Patients with Systemic Lupus Erythematosus. October 28, 2003.
(5) 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.
(6) 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.
(7) 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.
(8) 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.
(9) (HGSI Press Release) Human Genome Sciences Announces the Discovery of a Novel Immune Stimulant. July 8, 1999.
(10) (HGSI Press Release) High Levels of BLyS Implicated in Lupus and Rheumatoid Arthritis Patients. October 30, 2000.
(11) 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.
(12) 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.
(13) A role for BLyS in tissue inflammation? Carter RH. Arthritis & Rheumatism April 2003; 48(4): 882-885.
(14) 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.
(15) BLyS Plasma Concentrations Correlate with Disease Activity and Levels of Anti-dsDNA Autoantibodies and Immunoglobulins in a SLE Patient Observation Study. Petri M, Stohl W, Chatham W, McCune J, Butler T, Ryel J, Zhong J, Recta J, Freimuth W. Presentation to 67th Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals. October 2003.
(16) Biomarkers in SLE: The Hopkins lupus cohort. Petri M. Lupus Foundation of America Biomarkers for the Assessment of Systemic Lupus Erythematosus Meeting. March 2003.
(17) TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. Impaired B cell maturation in mice lacking BLyS. Gross J, Dillon S, Mudri S, et al. Immunity 2001 15(2): 289-302.
(18) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. Edwards JCW, Szczepanski L, Szechinski J, et al. New England Journal of Medicine. 2004; 350(25): 2572-2581.
(19) Baker KP, Edwards BM, Main SH et al. Generation and Characterization of LymphoStat-B, a Human Monoclonal Antibody That Antagonizes the Bioactivities of B-Lymphocyte Stimulator. Arthritis & Rheumatism 2003; 48: 3253-3265.

Source: Human Genome Sciences, Inc.

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