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Enrollment Complete for LymphoStat-B Trial in Rheumatoid Arthritis

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 rheumatoid arthritis.

The double-blind, placebo-controlled, multi-center Phase 2 clinical trial is designed to evaluate the safety, optimal dosing, and efficacy of LymphoStat-B in patients with rheumatoid arthritis(1). A total of 283 patients with active moderate-to-severe rheumatoid arthritis who have failed prior treatment have been enrolled in the trial and randomized to receive one of three different doses of either LymphoStat-B or placebo over a 24-week treatment period, in addition to standard-of-care therapy. Efficacy will be evaluated according to the American College of Rheumatology (ACR) criteria for defining clinical improvement in rheumatoid arthritis patients. The primary efficacy endpoint for the LymphoStat-B Phase 2 study will be the rate of response at week 24 (i.e., the percentage of patients who achieve at least 20% improvement on the ACR-specified measures of disease activity). Safety, pharmacokinetics, and changes in quality of life are being evaluated as well.

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 systemic lupus erythematosus (the subject of a separate press release distributed today)(2).

James D. McKay, D.O, F.A.C.R., F.A.C.O.I, Clinical Associate Professor of Medicine, Oklahoma State University Center for Health Science (Tulsa), said, "Several million people are afflicted by rheumatoid arthritis worldwide. It is a systemic, chronic autoimmune disease characterized by inflammation of the membrane lining the joint. Symptoms typically appear during middle age and may include swelling of the joints, difficulty moving, and daily joint pain that frequently interferes with a person's ability to conduct normal activities. Very good treatment options have become available over the past several years. However, a substantial subset of patients remains for whom these new treatments do not work, and toxicities must be managed carefully. New treatments are needed that can help control disease progression and improve the quality of life for those who suffer from rheumatoid arthritis. We look forward to investigating LymphoStat-B's potential role as a therapeutic option for the treatment of rheumatoid arthritis."

Mark Genovese, M.D., Associate Professor of Medicine, Division of Rheumatology, Stanford University School of Medicine, said, "Both retrospective and prospective studies have shown that BLyS protein levels are elevated in the blood and joint fluid of patients with rheumatoid arthritis, and may contribute to the production of autoantibodies(3,4,5,6). The presence of autoantibodies, especially rheumatoid factor, appears to correlate with disease severity(7,8,9). Because LymphoStat-B has been shown to inhibit BLyS function, it is believed that LymphoStat-B may reduce B-cell activation and autoantibody levels, and thereby may provide a therapeutic benefit to patients with rheumatoid arthritis."

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 rheumatoid arthritis, which remains an area of unmet medical need. The Phase 2 study will evaluate LymphoStat-B's safety, optimal dosing, and efficacy in the treatment of rheumatoid arthritis. 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 in this indication. We have met with a high level of interest among clinical investigators, and we expect that results will be available in the Spring of 2005."

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(10,11). Plasma B cells produce antibodies, the body's first line of defense against infection. In rheumatoid arthritis, lupus, 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(4,5,6,12,13,14,15). Preclinical and clinical studies demonstrate that B-cell antagonists can reduce autoantibody levels and help control rheumatoid arthritis disease activity(6,16,17).

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)(18). Clinical and preclinical studies indicate that LymphoStat-B is well tolerated and capable of reducing levels of antibody- producing B cells(19,20,21).

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.

For more information on LymphoStat-B, see https://www.gsk.com/. For more information on rheumatoid arthritis, lupus, or autoimmune diseases, visit the Arthritis Foundation at https://www.arthritis.org/, the National Institute of Arthritis and Musculoskeletal and Skin Diseases at https://www.niams.nih.gov/, or The Lupus Foundation of America at http://www.lupus.org/".

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.

Footnotes:
(1) (HGSI Press Release) Human Genome Sciences Initiates Phase 2 Clinical Trial of LymphoStat-B for the Treatment of Rheumatoid Arthritis. January 8, 2004.
(2) (HGSI Press Release) Human Genome Sciences Completes Patient Enrollment in a Phase 2 Clinical Trial of LymphoStat-B for the Treatment of Systemic Lupus Erythematosus. July 29, 2004.
(3) 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.
(4) A role for BLyS in tissue inflammation? Carter RH. Arthritis & Rheumatism April 2003; 48(4): 882-885.
(5) 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.
(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) B-cells, be gone -- B-cell depletion in the treatment of rheumatoid arthritis. Tsokos, G. New England Journal of Medicine. 2004; 350(25): 2546-2548.
(8) Rheumatoid factor measured by fluoroimmunoassay: a responsive measure of rheumatoid arthritis disease activity that is associated with joint damage. Knijff-Dutmer E, et al. Annals of Rheumatoid Disease. 2002; 61: 603-607.
(9) Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis. Bukhari M, et al. Arthritis & Rheumatism. 2002; 46(4): 906-912.
(10) BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Moore PA, Belvedere O, Orr A, et al. Science. 1999; 285: 260-263.
(11) (HGSI Press Release) Human Genome Sciences Announces the Discovery of a Novel Immune Stimulant. July 8, 1999.
(12) 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.
(13) 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.
(14) 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.
(15) (HGSI Press Release) High Levels of BLyS Implicated in Lupus and Rheumatoid Arthritis Patients. October 30, 2000.
(16) 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.
(17) 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.
(18) Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B-Lymphocyte Stimulator. Baker KP, Edwards BM, Main SH et al. Arthritis & Rheumatism 2003; 48: 3253-3265.
(19) (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.
(20) Safety, pharmacokinetic and pharmacodynamic results of a Phase 1 single and double dose-escalation study of LymphoStat-B (human monoclonal antibody to BLyS) in SLE patients. Furie R, Stohl W, Ginzler E, et al. 67th Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals. October 26, 2003. Abstract # 922.
(21) Effects of LymphoStat-B, a BLyS antagonist, when administered intravenously to cynomolgus monkeys. Halpern W, Lappin P, Zanardi T, et al. 67th Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals. October 27, 2003. Abstract # 1537.

Source: Human Genome Sciences, Inc.

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