Lupus drought: 50 years and counting

October 8, 2009 – 11:58 am by Michael Christel

In this month’s issue of R&D Directions, we examine the 10 most active areas of therapeutic research, and also highlight some promising therapies for diseases in these categories. One condition researchers are particularly hesitant to lump into that “promising” group is lupus – and who could blame them? There have been a grand total of zero new drugs approved for the potentially deadly autoimmune disease in the last 50 years, leaving drugmakers gun-shy when it comes to pursuing clinical research in this area.

Nevertheless, as far as specialty diseases go, lupus continues to be an appealing target for large drug developers eager to score the market’s first real product, and is championed actively by organizations such as the Lupus Foundation of America. Earlier this week, a nine-month study commissioned by the LFA was released, which spotlights the disease’s half-century treatment drought while also urging key stakeholders to adopt new recommendations to boost lupus R&D.

Lupus is a chronic, severe autoimmune disease that affects about 1.5 million Americans, primarily women ages 15 to 45, according to the U.S. Department of Health & Human Services. In its more severe form, lupus can lead to kidney failure, heart attack, atherosclerosis, or even death. The disease is believed to contribute to the production of autoantibodies, which cause the immune system to attack healthy cells and tissues by mistake, damaging joints, skin, blood vessels, hearts, and lungs. 

According to healthcare consulting firm The Lewin Group, which conducted the study, lupus “stands apart” from other chronic autoimmune diseases because the majority of therapies presently used to effectively manage lupus have not been approved by FDA for the disease. These drugs often have side effects that can be worse than the primary disease. They can include osteoporosis, weight gain, high blood pressure, diabetes, sterility, liver damage, and the increased risk of infection.

Despite the industry’s long history of drug failures for lupus, Human Genome Sciences Inc. and GlaxoSmithKline’s late-stage monoclonal antibody Benlysta has revived hopes in recent months. The drug specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, which 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.

Last month, the journal Arthritis Care & Research published an article describing the primary endpoint for Benlysta’s Phase III trials as a potentially significant advance in lupus drug development. In July, results from an 865-patient study, known as Bliss-52, found that Benylsta was more effective at easing pain, hair loss, and skin rash than placebo.

HGS and GlaxoSmithKline plan to apply for U.S. and European approval to sell Benlysta in the first half of 2010, should the drug succeed in its next Phase III trial.

Another potential treatment for lupus in the works is UCB and Immunomedics Inc. drug epratuzumab, the most advanced pipeline program in UCB’s immunology disease portfolio. In late August, data from a 12-week, Phase IIb dose and regimen-ranging study demonstrated clinical meaningful treatment effect of epratuzumab over placebo in lupus patients. Epratuzumab is a humanized anti-CD22 monoclonal antibody with the potential to modulate plasma B cell activity.

Cytoxan, approved in 1959 as a cancer therapy, has been used for a long time to treat lupus kidney disease. Cytoxan is administered intravenously and is sometimes used in combination with steroids or other drugs. The medicine is sold generically.

Tags: antibodies, autoimmune, Benlysta, lupus