Human Genome Sciences, Inc. (ROCKVILLE, Md.) announced that dosing has begun in BLISS-52, the second of two pivotal phase III clinical trials of LymphoStat-B® (belimumab), a human monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS®), in patients with active systemic lupus erythematosus (SLE). Dosing in BLISS-76, the first phase III trial of LymphoStat-B, began in February 2007. LymphoStat-B is being developed by HGS and GlaxoSmithKline (GSK) under a co-development and commercialization agreement entered into in August 2006.

The two double-blind, placebo-controlled, multi-center superiority trials will evaluate the efficacy and safety of LymphoStat-B plus standard-of-care, versus placebo plus standard-of-care, in patients with serologically active SLE. Each of the phase III trials will enroll approximately 810 patients, making this the largest double-blinded clinical development program ever undertaken in lupus patients. 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. BLISS-52 is being conducted primarily in Asia, South America and Eastern Europe. BLISS-76 is being conducted primarily in North America and Europe. Both trials are expected to complete patient enrollment in 2008. The US FDA and the European Agency for the Evaluation of Medicinal Products have agreed that the phase III trial design is suitable to support regulatory submissions and potential approval for marketing. The results of previous studies suggest that LymphoStat-B significantly reduced SLE disease activity in serologically active patients.

The primary efficacy endpoint of BLISS-52 and BLISS-76 is the patient response rate at Week 52, as defined by: (1) a reduction from baseline of at least 4 points on the SELENA SLEDAI disease activity scale, (2) 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), and (3) 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 trials, patients will be randomized to one of three treatment groups: 1 mg/kg LymphoStat-B, 10 mg/kg LymphoStat-B, or placebo. Patients will be dosed intravenously on Days 0, 14 and 28, then every 28 days for the duration of the study. All will receive standard-of-care in addition to study medications.

BLyS is a naturally occurring protein discovered by HGS that is required for the development of B-lymphocyte cells into mature plasma B-cells. In lupus, rheumatoid arthritis and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies, and 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.

LymphoStat-B was generated by HGS through 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, in which the FDA provides companies with more extensive feedback to improve the efficiency of the drug development and approval process.

HGS has responsibility for conducting the LymphoStat-B phase III trials, with assistance from GSK. The companies will share equally in phase III/IV development costs, sales and marketing expenses and profits of any product commercialized under the agreement.

—A. Techman

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