Human Genome Sciences, Inc. Says Lupus Drug Shows Promise
"The substantial evidence now available from our Phase 2 clinical program clearly supports the Phase 3 study of LymphoStat-B in patients with systemic lupus erythematosus," said David C. Stump, M.D., Executive Vice President, Drug Development, Human Genome Sciences. "We have also learned a great deal from the data presented at EULAR about the clinical endpoints available for the evaluation of new therapies for SLE, and about the specific nature of their interaction with LymphoStat-B in lupus patients. These results will guide the design of the Phase 3 trial of LymphoStat-B that we and our collaborator, GlaxoSmithKline, expect to initiate in 2006. We look forward to the opportunity to advance the development of what we believe will become an important therapeutic option for patients suffering from this debilitating disease."
"The Phase 2 study results demonstrate that LymphoStat-B is safe and well tolerated, shows bioactivity across all doses studied, and reduces SLE disease activity as evidenced by significant changes in multiple biomarkers and clinical indicators. Further evaluation of LymphoStat-B for the treatment of SLE in Phase 3 clinical trials is warranted," said Daniel J. Wallace, M.D., Clinical Professor of Medicine, David Geffen School of Medicine, UCLA (based at Cedars-Sinai Medical Center, Los Angeles).
"A potential patient response endpoint for the development of new drugs to treat SLE has emerged from the Phase 2 trial of LymphoStat-B," said Richard Furie, M.D., Chief, Division of Rheumatology and Allergy-Clinical Immunology, North Shore Long Island Jewish Health System, Lake Success, NY, and Associate Professor of Medicine, New York University School of Medicine. "This response rate includes elements of the SELENA SLEDAI and BILAG disease activity indices, as well as the Physician's Global Assessment. These measures are well known to clinical investigators with experience in SLE. The results presented today show that LymphoStat-B significantly reduced disease activity versus the current standard of care in serologically active patients, based both on this combined response rate and on more traditional singular measures such as the SELENA SLEDAI, the SF-36 quality of life assessment, and the Physician's Global Assessment."
About the Phase 2 Trial Results
The Phase 2 study was designed as a randomized, double-blind, placebo-controlled, dose-ranging superiority trial to evaluate the safety, tolerability and efficacy of LymphoStat-B plus standard of care, versus placebo plus standard of care. The data presented demonstrate that LymphoStat-B was safe and well tolerated, and produced statistically significant reductions in disease activity versus placebo, as measured by:
* A significant reduction in anti-dsDNA autoantibodies among patients positive for anti-dsDNA at baseline (p<0.01 at Weeks 4-12: p<0.03 at Weeks 16-24, and p<0.01 at Weeks 32-52); * Significant reductions in immunoglobulins - IgG, IgE, IgM and IgA (p value less than or equal to 0.02 at Weeks 4-52); * Significant reductions in B-cell subsets, including CD19+ B-cells (p<0.01 at Weeks 8-52), CD20+/CD69+ activated B-cells (p<0.01 at Weeks 8-52), CD20+/CD27- naive B-cells (p<0.01 at Weeks 8-52), and CD20+/CD138+ plasmacytoid cells (p<0.01 at Weeks 16-52); * A significant increase in C4 complement at Weeks 4-52 among patients with low C4 complement at baseline (p value less than or equal to 0.01); * A significant reduction in the risk of SLE flares from Weeks 24-52 (p=0.04); * A significant reduction in SLE disease activity at Week 52 in seropositive patients (baseline HEp-2 ANA greater than or equal to 1:80 and/or anti-dsDNA greater than or equal to 30 IU), as measured by both SELENA SLEDAI (p=0.04) and the Physician's Global Assessment (p<0.01); * Significant improvements in quality of life evident early in treatment of seropositive patients as measured by SF-36 (p<0.05 at Week 12 and p=0.04 at Week 52); * A significant reduction in the number of seropositive patients experiencing BILAG Neurological and Musculoskeletal organ domain flares at Week 52 (Neurological p=0.04; Musculoskeletal p<0.01), with favorable trends noted for the Cardiovascular-Respiratory, Renal and General organ domains; * A reduction in the frequency of seropositive patients transitioning from low-dose prednisone (less than or equal to 7.5 mg/day) to high-dose prednisone (>7.5 mg/day) (p<0.05 at Weeks 8-12, and 32-40); * A significantly improved response rate among seropositive patients at Week 52 as defined by an improvement in SELENA SLEDAI score of 4 points or greater, no BILAG worsening, and no worsening in Physician's Global Assessment (p<0.01).
A total of 449 patients with active SLE were randomized to receive one of three different doses of LymphoStat-B or placebo (1, 4 or 10 mg/kg) administered intravenously over a 52-week treatment period, in addition to standard-of-care therapy. Seropositive patients accounted for 72% (323/449) of the total Phase 2 study population. All patients in the study were dosed on Days 0, 14 and 28, then every 28 days for the remainder of the 52 weeks. 86% of the patients were receiving background prednisone therapy, either alone or in combination. The pre-specified primary efficacy endpoints, which as previously disclosed were not met, were the SELENA SLEDAI score at Week 24 and time to first SLE disease flare over 52 weeks (as defined by the SLE Flare Index). A number of pre-specified secondary efficacy and biological endpoints, as well as safety, also were evaluated. The study was conducted at multiple centers in the United States and Canada.
In addition to today's oral presentations, a poster will be presented at EULAR on Friday, June 23, which will describe the distinct patterns of lupus activity and peripheral biomarkers observed in seropositive patients compared with seronegative patients. Based on the published abstract, the authors (M. Petri et al) conclude that the differences observed suggest that SLE disease activity may be due to B-cell dysfunction, and suggest that B-cell directed therapies such as belimumab (LymphoStat-B) would be appropriate in seropositive patients.
About LymphoStat-B
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. Plasma B cells produce antibodies, the body's first line of defense against infection. 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. 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. The presence of autoantibodies appears to correlate with disease severity. Preclinical and clinical studies demonstrate that B-cell antagonists can reduce autoantibody levels and help control autoimmune disease activity. LymphoStat-B is a Human Genome Sciences drug, created through a collaboration with Cambridge Antibody Technology.
GlaxoSmithKline has exercised its option under a June 1996 agreement to develop and commercialize LymphoStat-B jointly with Human Genome Sciences. Under the terms of the agreement, GSK and Human Genome Sciences will share equally in Phase 3/4 development costs, and will share equally in sales and marketing expenses and profits of any product that is commercialized under the agreement, under a co-development and co-promotion agreement, the remaining terms of which are being negotiated by the parties.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic, life-threatening disease. Between 200,000 and 500,000 people are diagnosed with SLE in the United States alone. The Lupus Foundation of America estimates that approximately 1.5 million Americans suffer from various forms of lupus, including SLE. Lupus can occur at any age, but appears mostly in young people between the ages of fifteen and forty-five. About 90 percent of the individuals diagnosed with lupus are women. African American women are about three times more likely to develop lupus, and it is also more common in Hispanic, Asian and American Indian women. 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. For more information on lupus, visit the Lupus Foundation of America at http://www.lupus.org, or the National Institute of Arthritis and Musculoskeletal and Skin Diseases at http://www.niams.nih.gov.
About Human Genome Sciences
The mission of Human Genome Sciences is to discover, develop, manufacture and market innovative drugs that serve patients with unmet medical needs, with a primary focus on protein and antibody drugs.
For more information about Human Genome Sciences, please visit the Company's web site at http://www.hgsi.com. For more information on LymphoStat-B, visit http://www.hgsi.com/products/LSB.html. Health professionals or patients interested in inquiring about LymphoStat-B trials or any other study involving Human Genome Sciences products are encouraged to inquire via the Contact Us section of the company's web site, http://www.hgsi.com/products/request.html, or by calling us at (301) 610-5790, extension 3550.
HGS, Human Genome Sciences, BLyS and LymphoStat-B are trademarks of Human Genome Sciences, Inc.
Safe Harbor Statement
This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences' current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company's unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company's ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company's dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today's date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
Source: Human Genome Sciences, Inc.