The lupus community has anxiously been awaiting the FDA approval of Benlysta, the first new drug approved for systemic lupus erythematosus (SLE) in 50 years. With last week's approval, there's cause for celebration. Belimumab was developed as a monoclonal antibody therapy by Human Genome Sciences, a biotechnology company with headquarters in Rockville Maryland, in collaboration with the UK pharmaceutical company GlaxoSmithKline.
Rather than targeting symptoms, belimumab is directed at the cause of the disease by its actions on the immune system.. Consequently, while improvement in symptoms may not show up for several months, the disease course is expected to become more benign. Symptoms are the result of organ damage caused by lupus autoantibodies, and belimumab works to inhibit production of these antibodies. Inhibiting autoantibody production is key for treating autoimmune disorders right at the source, allowing the disease to move into remission.
In autoimmune disorders, autoantibodies, once produced, remain in the blood circulation for two to three months before they’re broken down into amino acids and excreted. Consequently a decline in autoantibody production caused by the initial use of belimumab can’t immediately reduce autoantibody titers and symptoms. However, after the initial decline in autoantibodies, with continued drug therapy, low autoantibody titers will persist and symptoms will correspondingly decline.
Manipulating the Immune Response
Systemic lupus and many other autoimmune diseases are caused by an erratic immune system response in which a weak, ineffective immune system mistakenly attacks the body’s own cells. In lupus, the immune system produces a number of different antinuclear antibodies (ANA) that damage functional cells. A systemic autoimmune disease, lupus affects multiple organs, including the joints, kidneys, heart, lungs, and skin.
Belimumab is a synthetic antibody that binds to and inhibits a naturally occurring protein, the B-lymphocyte stimulator (BLyS). By blocking BLyS, belimumab prevents B-lymphocytes from producing the autoantibodies responsible for the disease process.
Making History
When belimumab successfully hurdled its way through two large phase III trials in 2009, it was the first lupus drug to make this claim. Its development can be credited to the genomics movement that started in the late 1990s. With advances in gene technology, researchers learned how to manipulate white blood cells in ways that affected immune function. Development of two earlier therapeutic antibody compounds ocrelizumab and atacicept, were halted when test subjects showed an increase tendency to develop infections, especially when used in combination with other lupus drugs that suppress the immune system. Fortunately, belimumab has not been associated with any troublesome side effects.
While belimumab is the first of this new generation of drug therapies for lupus, other promising compounds are under investigation and expected to also make their way into the U.S. Pharmacopeia. These include BLyS inhibitors in development by Athera in Hayward, California, and Eli Lilly in Indianapolis, Indiana. Research is also underway that targets other immune system proteins. For instance, Amgen, located in Thousand Oak, California is developing two antibody therapies for lupus, one which targets T-lymphocytes by inhibiting B7-related protein, and the other by inhibiting the pro-inflammatory cytokine interferon-gamma.
Dosing information as well as complete information about Benlysta are available at the official Benlysta website.
Resource:
Heidi Ledford, 2011. "First lupus drug in half a century approved." Nature, March doi:10:10.1038/news.2011.150
Elaine Moore - I'm a retired medical technologist and medical writer with more than 30 years experience working in hospital laboratories. Currently, I ...
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