After a 50-year drought of new drugs and a string of disappointing failures of potential treatments for lupus, researchers said Monday that they have found an experimental drug that can ameliorate the symptoms of the life-threatening autoimmune disorder that afflicts as many as 1.5 million Americans.
In unpublished results released by the company, a team from Human Genome Sciences said that the experimental drug Benlysta significantly reduced lupus symptoms in a randomized trial of more than 850 patients, reducing their need for debilitating steroids and improving quality of life.
In recent years, at least seven companies or coalitions of companies have reported failed or unimpressive results with potential lupus treatments, causing a cloud of gloom to settle over the lupus community.
"We have had many disappointments, so for [a drug] to make it through the door with a very significant success rate is an extraordinary accomplishment," said Margaret G. Dowd, president of the Lupus Research Institute, who was not involved in the research. Not only does the trial offer lupus patients the hope of a new treatment with fewer side effects, she said, but it should also offer encouragement to other companies with lupus drugs in the pipeline.
"Everybody was getting a little discouraged," added Dr. Betty Diamond, chief of the autoimmune disease center at North Shore-Long Island Jewish Health System's Feinstein Institute for Medical Research in Manhasset, N.Y., who was also not involved in the research. "It's very exciting to finally have a trial in lupus showing efficacy.
"We're going to have to work with it longer to understand when it should be used and exactly who is going to benefit from it . . . but we are very pleased to have a drug that looks as though it really did do something," said Diamond, who is an advisor to the Lupus Research Institute.
Experts cautioned, however, that because the results have not been peer-reviewed or published in a journal, it is difficult to fully assess their significance. Human Genome Sciences said the results will be presented at a meeting later this year and published after a second study is completed. A spokesman said the robust nature of the data and the 50-year drought in drugs justified releasing the data now.
Lupus is a chronic inflammatory disease that occurs when the body's immune system attacks its own tissues and organs. As many as 90% of patients are women, usually in their 30s and 40s when it first strikes. No two cases of lupus are identical, but symptoms can include fatigue, fever, joint pain, stiffness and swelling, rashes, skin lesions, mouth sores, hair loss and chest pain. The disease can attack many internal organs, leading eventually to death.
Only three drugs are approved for treating lupus -- aspirin, the steroid prednisone and the antimalarial drug Plaquenil (hydroxychloroquine) -- and all were approved during the Eisenhower administration. All can have severe side effects, including stomach bleeding for aspirin; weight gain, bruising, high blood pressure and diabetes for prednisone; and vision problems and muscle weakness for Plaquenil.
Even more powerful drugs are often used off-label for treating severe cases, including the anti-rejection drugs cyclophosphamide and azathioprene, which can have even more serious side effects.
Benlysta is a monoclonal antibody known generically as belimumab. An immune protein produced artificially, it binds to and blocks the activity of a protein called B-lymphocyte stimulator, which was discovered by the company. Elevated levels of B-lymphocyte stimulator are believed to contribute to the production of antibodies that attack the patient's own organs.
The new trial was conducted in 865 patients at 90 sites in 13 countries, primarily abroad. Patients all had active lupus, although none had a severe form requiring hospitalization, and received normal care for the disease. In addition, they were randomized into three groups, two receiving different amounts of the drug and the third receiving a placebo. Patients were given an infusion of the drug at the beginning of the trial, at two weeks, at four weeks, and then every four weeks after that. They were followed for 52 weeks.
About 58% of patients receiving the highest dose of Benlysta showed a significant improvement on an index used to assess impact, compared with 46% of those receiving the placebo. More of the patients receiving the drug were able to reduce their prednisone intake, and most reported a better quality of life, although specific numbers were not provided.
About 6% of both patients receiving the drug and those on the placebo suffered side effects, including headache, joint pain and infections.
The patients receiving the drug showed the improvement while reducing their use of steroids, said Dr. Kenneth Kalunian of UC San Diego, who was not involved in the study. "The fact that they could taper off steroids in the drug group really speaks well for the drug." Dr. Daniel Wallace of UCLA's Geffen School of Medicine treated patients with the drug in an earlier study and has been continuing to treat them, some for as long as four years. "They keep getting better and better," he said. "This is going to be a major breakthrough, no question about it."