Human Genome Sciences, Inc. (HGSI) announced that it has submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for approval to market Benlysta (belimumab) for the treatment of systemic lupus erythematosus (SLE).

The BLA submission includes the results of two pivotal phase 3 clinical trials in autoantibody-positive patients with SLE showing that belimumab met its primary endpoint. In the phase 3 studies, known as BLISS-52 and BLISS-76, belimumab 10 mg/kg plus standard of care achieved a statistically significant improvement in patient response rate as measured by the SLE Responder Index at Week 52, compared with placebo plus standard of care. Study results also showed that belimumab was generally well tolerated in BLISS-52 and BLISS-76, as demonstrated by a similar rate of discontinuations due to adverse events across treatment groups, with overall adverse event rates comparable between belimumab and placebo treatment groups. The design of the two trials was similar, but the duration of therapy in the two studies was different – 52 weeks for BLISS-52 and 76 weeks for BLISS-76. HGS designed the phase 3 programme for belimumab in collaboration with GlaxoSmithKline (GSK) and leading international SLE experts, and in consultation with the FDA. The two studies treated a total of 1,684 patients.

“We and GSK have now submitted regulatory applications for Benlysta in both the United States and Europe,” said H. Thomas Watkins, president and chief executive officer, HGS. “Our companies will continue to work together to achieve licensure and bring this potentially important new therapeutic option to market. Based on the results of our pivotal Phase 3 studies, HGS believes Benlysta could become the first new approved drug for systemic lupus in more than 50 years.”

Belimumab is being developed by HGS and GSK under a co-development and commercialization agreement entered into in 2006. GSK submitted a Marketing Authorization Application for belimumab to the European Medicines Agency (EMA) on June 4, 2010.

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 survival and maturation of B-lymphocyte cells into 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. The results of two pivotal Phase 3 trials, BLISS-52 and BLISS-76, suggest that belimumab can reduce SLE disease activity.
About the HGS/GSK Collaboration

In 2006, HGS and GSK entered into a definitive co-development and commercialization agreement under which HGS has conducted 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 agreement.

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 per cent 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.