Human Genome Sciences, Inc. said it has completed enrolment and initial dosing in BLISS-52, one of two pivotal phase III clinical trials of LymphoStat-B (belimumab) in patients with active systemic lupus erythematosus (SLE). LymphoStat-B is being developed by HGS and GlaxoSmithKline (GSK) under a co-development and commercialisation agreement entered into in August 2006.
"We continue to be excited by LymphoStat-B's potential. Assuming it is successful in phase III, we believe that LymphoStat-B could represent a breakthrough in the treatment of SLE," said H. Thomas Watkins, president and chief executive officer, HGS. "With enrolment now completed in the BLISS-52 trial, we are on track to have our first phase III data for LymphoStat-B available by mid-2009, and all phase III data available in fall 2009."
BLISS-52 was initiated in May 2007, and has enrolled and randomised a total of 867 patients at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe. Completion of enrolment for the other pivotal Phase 3 trial of belimumab, BLISS-76, is expected by the end of summer 2008. BLISS-76, which was initiated in February 2007, is being conducted primarily in North America and Europe, and will enrol and randomise a minimum of 810 subjects.
"The results of previous studies suggest that belimumab significantly reduced SLE disease activity in serologically active patients," said Professor Sandra V Navarra, M.D., a principal investigator and head of Rheumatology at the University of Santo Tomas, Manila, Philippines. "There is a great need for better tolerated and more effective treatments for lupus, and we look forward to seeing the first phase III data for belimumab by mid-2009."
The LymphoStat-B phase III development programme includes two double-blind, placebo-controlled, multi-centre phase III superiority trials - BLISS-52 and BLISS-76 - to evaluate the efficacy and safety of LymphoStat-B plus standard of care, versus placebo plus standard of care, in patients with serologically active SLE. 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 (BLA). HGS designed the LymphoStat-B phase III programme in collaboration with GSK and leading international SLE experts.
"A total of nearly 1700 patients worldwide will be enrolled and randomized in the phase III trials of belimumab, making this the largest double-blinded clinical development program ever undertaken in lupus patients," said William W. Freimuth, M D, Ph,D., vice president, clinical research - immunology, rheumatology and infectious diseases, HGS. "Today's milestone brings us closer to seeing phase III data that we hope will confirm belimumab's promise as a potential treatment for patients with SLE. We are grateful for the superb performance of our clinical investigators, whose diligence made it possible to complete the enrolment of BLISS-52 ahead of our fall 2008 projection."
The primary efficacy endpoint of BLISS-52 and BLISS-76 is the patient response rate at Week 52, as defined by: A reduction from baseline of at least 4 points on the Selena Sledai disease activity scale; no worsening of disease as measured by the Physician's Global Assessment (worsening defined as an increase of more than 0.30 points from baseline); no new BILAG A organ domain score (which would indicate 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 each of the two phase III trials, patients are randomized to one of three treatment groups: 1 mg/kg belimumab, 10 mg/kg belimumab, or placebo. Patients are dosed intravenously on Days 0, 14 and 28, then every 28 days for the duration of the study. All receive standard of care therapy in addition to study medication. Safety and tolerability are evaluated by an independent Data Monitoring Committee throughout both studies.
LymphoStat-B (belimumab) 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 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 defence against infections. 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. Pre-clinical and clinical studies demonstrate that B-cell antagonists can reduce autoantibody levels and help control autoimmune disease activity.