A new type of experimental drug appears promising for treating two devastating illnesses caused by the immune system attacking parts of the body -- multiple sclerosis and Crohn's disease.
The drug, called Antegren, significantly reduced the number of new brain lesions and relapses in patients suffering from multiple sclerosis (MS), and improved the conditions of patients suffering from Crohn's, an intestinal disease, according to two studies published together today.
The findings suggest that a new strategy for controlling the immune system, designed to be more targeted than existing approaches, could provide a better means of treating so-called autoimmune diseases such as MS, Crohn's and rheumatoid arthritis.
"It's very exciting," said Lars Ekman, president of research and development for Elan Pharmaceuticals of Dublin, Ireland, which is developing Antegren with Biogen Inc. of Cambridge, Mass. "It's one of the first times a molecule with a new mechanism of action shows efficacy in two apparently very different diseases. It's a new treatment paradigm for autoimmune diseases."
The drug has also shown promise in a small, still unpublished study for treating ulcerative colitis, another autoimmune disease, Ekman said.
Autoimmune diseases are a class of illnesses in which the immune system attacks the body for reasons that remain unclear. In MS, which afflicts an estimated 400,000 Americans, the immune system attacks the coating around nerve cells in the brain and spinal cord, causing an often progressive, crippling loss of motor control. In Crohn's, the immune system attacks cells lining the intestines, and causes severe abdominal pain, fever, ulcers and other problems that can become disabling. As many as 1 million Americans suffer from Crohn's or ulcerative colitis.
Although there are a handful of treatments for the diseases, none are very effective and all can have side effects.
Antegren, also known as natalizumab, is a laboratory-produced protein called a monoclonal antibody. It is the first of a new class of compounds known as selective adhesion molecule (SAM) inhibitors because they are designed to inhibit the ability of certain immune cells to adhere to cells in parts of the body that are being damaged. Researchers hope the approach will be more effective and produce fewer side effects than existing medications, which tend to dampen down the immune system overall.
Antegren selectively blocks key white blood cells called lymphocytes from attaching to proteins known as alpha-4 integrins, which is how the lymphocytes get to different parts of the body -- into the central nervous system in MS and into digestive system tissue in Crohn's.
The new studies involved 248 patients with Crohn's in Europe and 213 patients in the United States, Canada and Britain with the most common form of MS, known as relapsing remitting, or secondary progressive MS. The patients received either a placebo or different doses of Antegren. After six months, brain scans and other tests showed that patients receiving the drug had about a 90 percent reduction in brain lesions and about half as many relapses, researchers reported in today's New England Journal of Medicine. Crohn's patients receiving the drug had about twice the remission rate of those receiving a placebo, researchers reported. There were no significant serious side effects.
"What's exciting is the different mode of action. It's attacking the problem at a different location. It's highly specific, as opposed to more general," said Patricia O'Looney, director of research and medical programs at the National Multiple Sclerosis Society. "This study demonstrates that this is a reasonable approach."
It may turn out that the drug is most effective when combined with other medications, O'Looney said.
Subrata Ghosh of the Imperial College of London, who conducted the Crohn's study, likened the drug to a "small missile," because it's "more specific and targeted."
In a commentary accompanying the articles, Ulrich H. von Andrian of the Harvard Medical School in Boston and Britta Engelhardt of the Max Planck Institute for Vascular Biology in Muenster, Germany, cautioned that longer, larger studies are needed to fully evaluate the drug.
Studies involving several thousand patients are already underway to confirm the drug's effectiveness for both diseases, Ekman said. The companies hope to have enough data to apply for Food and Drug Administration approval by the end of 2003, he said.