From Our Archives
Medical Author: Melissa Stoppler, M.D.
Medical Editor: Barbara K. Hecht, Ph.D.
Marketing has been suspended for a new drug that reduced relapses among people with multiple sclerosis (MS). This important action was taken after reports of two serious adverse events in persons receiving therapy with the new drug which is called Tysabri (natalizumab).
Multiple sclerosis is a common chronic disease of the nervous system. The symptoms tend to become evident between age 20 and 50. These symptoms reflect inflammation and destruction of the myelin sheath, the protective covering that surrounds and insulates nerves. When myelin is damaged, the nerves eventually become damaged, leading to disrupted transmission of signals within the nervous system.
A multiple sclerosis patient typically has the acute (sudden) onset of symptoms, which constitute an attack of multiple sclerosis. The symptoms are extremely variable and can range from mild to severe. Depending on which nerves are damaged, people with multiple sclerosis may have disturbances in vision, speech, walking, writing, or memory. Muscle spasms, fatigue, numbness, and prickling pain are also common symptoms along with a loss of sensation, dizziness, and occasionally hearing loss.
Attacks may be brief or continue for months to years. In the most common form of multiple sclerosis, attacks are followed by a complete or partial disappearance of the symptoms (remission) until another attack occurs (relapse).
While the exact cause of multiple sclerosis is unknown, it is generally thought that multiple sclerosis is an autoimmune disease. Exposure to a toxin or infectious agent early in life, for example, may trigger an abnormal response by the body's own immune system that leads to the progressive nerve damage.
The new drug, Tysabri, is a monoclonal antibody that interferes with certain functions of the immune response. (A monoclonal antibody is a pure antibody produced by a single clone of cells, in this case bioengineered in the laboratory.)
Given intravenously once a month, Tysabri was found to reduce the relapse rate of multiple sclerosis by two-thirds, according to a study at Rush University Medical Center in Chicago. In November 2004, Tysabri was given accelerated approval by the U.S. Food and Drug Administration (FDA) as a treatment for all relapsing forms of multiple sclerosis.
In March 2005 the FDA announced that Biogen Idec, the manufacturer of Tysabri, had voluntarily suspended marketing of the drug after reports had been received of one fatal case and one additional case of progressive multifocal leukoencephalopathy (PML), a serious progressive neurologic disease, in patients receiving Tysabri.
The FDA stated that "Discussions between the FDA, Biogen Idec, and scientific experts have begun in order to assess the potential association between Tysabri and PML, methods for early diagnosis of PML, and to determine whether multiple sclerosis patients who may be at particular risk can be identified."
Other adverse reactions to Tysabri include hypersensitivity reactions to the drug (including rare anaphylactic reactions) in less than 1% of cases. A slightly increased incidence of infections was also seen in those using Tysabri. Tysabri use is contraindicated in anyone who has a history of hypersensitivity reactions to the drug, and its safety for pregnant and nursing mothers has not yet been fully established.
Based on all available information and deliberations, it is expected that decisions will be made regarding the future usage of Tysabri. In the meantime, those taking Tysabri have been advised to discuss alternative treatments with their doctor.
Reference: Clinical Trial
"Safety and Efficacy of Natalizumab in the
Treatment of Multiple Sclerosis"
Study ID Numbers: C-1801
Identifier: NCT00027300 Health Authority: United States: Food and Drug Administration