Novel Evidence-Based SLE Responder Index Described In Peer Reviewed Publication As Potentially Significant Advance In Lupus Drug Development
Main Category: LupusAlso Included In: Clinical Trials / Drug Trials
Article Date: 07 Sep 2009 - 3:00 PDT
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Human Genome Sciences, Inc. (NASDAQ:HGSI) announced publication by the journal
"The lack of a gold standard to measure SLE disease activity endorsed by international rheumatology societies or national health authorities has impeded the development of SLE therapies," said Richard A. Furie, M.D., lead author of the article and Chief, Division of Rheumatology and Allergy-Clinical Immunology, North Shore Long Island Jewish Health System, Lake Success, NY, and Professor of Medicine, Albert Einstein College of Medicine. "In other diseases where manifestations are heterogeneous, combined responder instruments have been used to assess disease activity. We believe the SLE Responder Index may play an important role in drug development for this potentially devastating disease."
The primary efficacy endpoint of both Phase 3 trials of belimumab is the SLE Responder Index at Week 52, as defined by: (1) a reduction from baseline of at least 4 points on the SELENA SLEDAI disease activity scale (which indicates a clinically important reduction in SLE disease activity); (2) no worsening of disease as measured by the Physician's Global Assessment (worsening defined as an increase of 0.30 points or more from baseline); and (3) no new BILAG A organ domain score (which indicates a severe flare of lupus disease activity) and no more than one new BILAG B organ domain score (which would indicate a moderate flare of disease activity).
In July 2009, HGS and GSK announced that belimumab met this primary endpoint in BLISS-52, the first of the two Phase 3 trials. Results from BLISS-76, the second Phase 3 trial, are expected in November 2009. Belimumab is being developed by HGS and GSK under a co-development and commercialization agreement entered into in August 2006.
"The SLE Responder Index selected as the primary efficacy endpoint of the BLISS studies of belimumab emerged directly from exploratory analysis of the results of our Phase 2 clinical trial," said William W. Freimuth, M.D., Ph.D., Vice President, Clinical Research - Immunology, Rheumatology and Infectious Diseases. "This novel and robust index now allows clinical investigators to measure improvement in overall SLE disease activity while at the same time ensuring that the improvement is not accompanied by worsening in other disease manifestations such as organ flares. I am delighted that the validity of the endpoint has now been established with its successful prospective use in the recently completed BLISS-52 study."
About the BENLYSTA (belimumab) Phase 3 Development Program
The Phase 3 development program for belimumab includes two double-blind, placebo-controlled, multi-center Phase 3 superiority trials - BLISS-52 and BLISS-76 - to evaluate the efficacy and safety of belimumab plus standard of care, versus placebo plus standard of care, in serologically active (i.e., autoantibody-positive) patients with SLE. This is the largest clinical trial program ever conducted in lupus patients. BLISS-52 randomized and treated 865 patients at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe. BLISS-76 enrolled and randomized 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe. The design of the two trials is similar, but the duration of therapy in the two studies is different - 52 weeks for BLISS-52 and 76 weeks for BLISS-76. The data from BLISS-76 will be analyzed after 52 weeks in support of a potential Biologics License Application in the United States and Marketing Authorization Applications in Europe and other regions.
In each of the two Phase 3 trials, patients were randomized to one of three treatment groups: 10 mg/kg belimumab, 1 mg/kg belimumab, or placebo. Patients are dosed intravenously on Days 0, 14 and 28, then every 28 days thereafter for the duration of the study. All receive standard of care therapy in addition to the study medication. Analysis for the primary endpoint is based on intention-to-treat (ITT) and adjusted for baseline stratification factors, including SELENA SLEDAI score, proteinuria and race. Safety is reviewed by an independent Data Monitoring Committee throughout both studies.
About BENLYSTA (belimumab)
Belimumab is an investigational human monoclonal antibody drug that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS®. 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 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 suggest that belimumab can reduce autoantibody levels in SLE. BLISS-52 results suggest that belimumab can reduce SLE disease activity, and a second Phase 3 trial, BLISS-76, is underway to confirm these results.
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 belimumab 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 current agreement.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic, life-threatening autoimmune disease. Approximately five million people worldwide, including approximately 1.5 million in the United States, suffer from various forms of lupus, including SLE. Lupus can occur at any age, but appears mostly in young people ages 15 to 45. About 90 percent of those 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, the Lupus Research Institute at http://www.lupusresearchinstitute.org, the National Institute of Arthritis and Musculoskeletal and Skin Diseases at http://www.niams.nih.gov, or Lupus Europe at http://www.elef.rheumanet.org.
Source
Human Genome Sciences
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