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Results of Phase 1 Clinical Trial Demonstrate That LymphoStat-B(TM) Is Safe and Biologically Active in Patients with Systemic Lupus Erythematosus


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."



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