Healthcare Industry News: GSK
News Release - November 14, 2006
Human Genome Sciences Announces Positive 76-Week Results of Phase 2 Clinical Trial of LymphoStat-B(TM) in Systemic Lupus ErythematosusLymphoStat-B(TM) reduces signs and symptoms of SLE disease and demonstrates durable biological activity at 76 weeks
Phase 3 clinical trials to begin before year-end 2006
ROCKVILLE, Md., Nov. 14 (HSMN NewsFeed) -- Human Genome Sciences, Inc. (Nasdaq: HGSI ) announced today that the 76-week results of a Phase 2 clinical trial demonstrated that LymphoStat-B(TM) (belimumab) reduced disease activity in patients with serologically active systemic lupus erythematosus (SLE), exhibited durable biological activity, and appeared safe and well tolerated. In the LymphoStat-B treatment groups, the percentage of serologically active SLE patients who achieved the combined response rate selected as the primary efficacy endpoint for Phase 3 trials of LymphoStat- B(TM) increased from 46% at Week 52 to 56% at Week 76, with no increase in infections or infectious events observed over time.
The results were presented today in two oral presentations in Washington, DC at the 70th Annual Meeting of the American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP). Additional LymphoStat-B results were reported in poster presentations throughout the meeting.
"The data that have emerged from the 24-week extension of the Phase 2 trial of LymphoStat-B show continued improvement beyond the first 52 weeks of treatment," said Daniel J. Wallace, M.D., Clinical Professor of Medicine, David Geffen School of Medicine, UCLA (based at Cedars-Sinai Medical Center, Los Angeles). "The reductions we see in SLE biomarkers, as well as the improvements observed in health-related quality of life, appear to correlate with therapeutic response. In serologically active patients, LymphoStat-B significantly reduced SLE disease activity, as evidenced by changes in multiple biomarkers and clinical indicators, including the combined response rate chosen as the primary efficacy endpoint of the Phase 3 trials. We look forward to continuing its evaluation as a potential treatment for SLE."
"The results presented at this year's ACR/ARHP meeting confirm and extend the growing body of evidence that LymphoStat-B has the potential to help meet the significant unmet need that we see in the SLE patient population," said William W. Freimuth, M.D., Ph.D., Vice President, Clinical Research - Immunology, Rheumatology and Infectious Diseases, Human Genome Sciences. "We are encouraged that 96% of the patients who completed the 52-week Phase 2 study chose to participate in the 24-week extension phase. Many of these patients were first randomized into the trial as long as three years ago and continue on treatment today. This provides us with a substantial longitudinal safety data base as we prepare to initiate Phase 3 trials before the end of 2006."
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. 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. Serologically active patients accounted for 72% (323/449) of the total Phase 2 study population. 86% (386/449) of the patients were receiving background prednisone therapy, either alone or in combination. At Week 52, patients were offered the opportunity to participate in an optional 24-week extension phase. In the extension phase, all placebo patients received LymphoStat-B at a dose of 10 mg/kg, while patients in the LymphoStat-B 10 mg/kg treatment arm continued on the 10 mg/kg dose, and patients in the 1 mg/kg and 4 mg/kg LymphoStat-B treatment arms were offered the choice of continuing on the same dose or receiving LymphoStat-B at a dose of 10 mg/kg.
Of the patients who completed 52 weeks of treatment, 96% (351/364) elected to enter the 24-week extension phase of the trial, and 92% (321/351) of those who entered completed it. Of those completing the extension phase, 83% (265/321) continue to receive LymphoStat-B. The study began in October 2003.
In June 2006, HGS reported the full presentation of 52-week data from the Phase 2 trial of LymphoStat-B in patients with SLE. The 52-week results demonstrated that LymphoStat-B significantly reduced disease activity in patients with serologically active SLE, exhibited clinically relevant biological activity, and appeared safe and well tolerated. Among the Phase 2 study findings was a significantly improved response rate among serologically active 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 (46% for LymphoStat-B versus 29% for placebo, p<0.01). This combination of measures is the primary efficacy endpoint in the Phase 3 program design.
The data presented at the ACR/ARHP annual meeting demonstrated that LymphoStat-B continued to reduce the signs and symptoms of SLE disease activity throughout the 24-week extension phase of the study, demonstrated durable biological activity at Week 76, and appeared safe and well tolerated, with frequency and severity of adverse events similar to placebo and with no increase at higher doses. The evidence of continuing improvement from Week 52 to Week 76 includes:
-- An increase from 46% to 56% in the response rate among serologically active patients, as defined by an improvement in SELENA SLEDAI score of 4 points or greater, no worsening in Physician's Global Assessment (with worsening defined as an increase in PGA of more than 0.30 points), no new BILAG A organ domain score and no more than 1 new BILAG B organ domain score from baseline. This combination of measures at 52 weeks is the primary efficacy endpoint of the Phase 3 trials. -- An increase from 29% to 38% in the reduction in SLE disease activity among serologically active patients, as measured by SELENA SLEDAI. -- An increase from 33% to 41% among serologically active patients who showed no worsening in the Physician's Global Assessment. -- An increase in the mean improvement in health-related quality of life from 3.0 points to 3.4 points among serologically active patients, as measured by the SF-36 Physical Component Summary score. -- A durable reduction in anti-dsDNA autoantibodies (at least 50% or negative) among patients who were positive for anti-dsDNA at baseline (27% at Week 52; 28% at Week 76). -- Durable or increased reductions from Week 52 to Week 76 in B-cell subsets including total CD20+, naive (CD20+/CD27-), activated (CD20+/CD69+), and plasmacytoid (CD20+/CD138+). -- An increase in C4 complement among patients with low C4 complement at baseline (33% at Week 52; 46% at Week 76). -- Stable reductions in immunoglobulins, with no increase in infections or infectious events over time.
In addition, the 52-Week data showed that, in serologically active SLE patients, LymphoStat-B:
-- Significantly delayed the time to SLE flare after six months (p<0.04); -- Reduced the frequency of SLE flares after six months; -- Significantly reduced the frequency of 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 over multiple time-points); -- Significantly reduced the number of patients experiencing BILAG Neurological and Musculoskeletal organ domain flares at Week 52 (Neurological p=0.04; Musculoskeletal p<0.01; and Cardiovascular- Respiratory (p=0.06); and -- Produced significant and clinically meaningful improvements in health- related quality of life in serologically active SLE patients.
The 76-week results of the LymphoStat-B Phase 2 trial, as well as the results of other studies presented at the ACR/ARHP meeting, demonstrated that therapeutic responses in patients with active SLE, as measured by the combined response index selected as the primary efficacy endpoint of the LymphoStat-B Phase 3 trials, correlated well with changes in SLE biomarkers and improvements observed in health-related quality of life. In the Phase 2 study, relative to baseline, responders across all groups (LymphoStat-B and placebo) exhibited greater changes in biomarkers for SLE disease and reported more improvement in health-related quality of life than was observed in non- responders.
About the Collaboration with GSK
In August 2006, HGS and GSK entered into a definitive co-development and co-commercialization agreement under which HGS has responsibility for conducting the LymphoStat-B Phase 3 trials, with assistance from GSK. The companies will share equally in Phase 3/4 development costs, sales and marketing expenses, and profits of any product commercialized under the agreement.
LymphoStat-B is a human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS(TM). BLyS is a naturally occurring protein discovered by HGS 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. 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 demonstrated 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. It has received a Fast Track Product designation from the FDA for its potential use in treating SLE and has been selected for participation in the FDA's Continuous Marketing Application Pilot 2 Program.
For links to scientific presentations and posters referenced, or for more information about LymphoStat-B, visit http://www.hgsi.com/products/LSB.html.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic, life-threatening disease. The Lupus Foundation of America estimates that approximately 1.5 million Americans suffer from various forms of lupus, including SLE. More than 300,000 people are afflicted with SLE in the United States alone. 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.
The HGS clinical development pipeline includes drugs to treat hepatitis C, lupus, anthrax disease, cancer, rheumatoid arthritis and HIV/AIDS. The Company's primary focus is rapid progress toward the commercialization of its two lead compounds, Albuferon(TM) for hepatitis C, and LymphoStat-B(TM) for lupus. Both compounds are expected to advance to Phase 3 clinical trials in 2006.
In June 2006, HGS announced that the U.S. Government exercised its option under an existing contract to purchase 20,000 doses of ABthrax(TM) for the treatment of anthrax disease. Other HGS compounds in clinical development include three TRAIL receptor antibodies for the treatment of hematopoietic and solid malignancies, in addition to an antibody to the CCR5 receptor for the treatment of HIV/AIDS.
For more information about HGS, please visit the Company's web site at http://www.hgsi.com. Health professionals or patients interested in inquiring about LymphoStat-B clinical trials or any other study involving HGS products in development 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, ABthrax, Albuferon, 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. In addition, the Company will continue to face risks related to animal and human testing, to the manufacture of ABthrax and to FDA concurrence that ABthrax meets the requirements of the ABthrax contract. If the Company is unable to meet the product requirements associated with the ABthrax contract, the U.S. Government will not be required to reimburse the Company for the costs incurred or to purchase any ABthrax doses. 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
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