Editor’s Update: On February 28, 2005, Biogen Idec and Elan announced a voluntary suspension of the marketing of TYSABRI. Patients with TYSABRI questions should contact their physician.
The government has given approval to a new therapy for relapsing forms of multiple sclerosis (MS). The drug, known as natalizumab, and branded as Tysabri, is indicated as a treatment for relapses, or exacerbations.
"Tysabri is a significant breakthrough for patients with MS," said Kelly Martin, president and CEO of Elan, which co-produced the drug with Biogen Idec. "The approval of Tysabri, with its unique mechanism of action and new level of efficacy, has the potential to make a genuine difference in the lives of patients and families who struggle with the debilitating effects of this disease."
Clearly-Defined Flare-Ups
Relapsing-remitting MS is the most common form of the disease, affecting about 85 percent of the people who have it. This form is characterized by clearly defined relapses (also known as flare-ups or attacks) which include episodes of acute worsening of neurologic function. This is followed by partial or complete recovery periods free of disease progression.1
Tysabri is a monoclonal antibody designed to prevent cells that make up the immune system in the bloodstream from migrating to the brain and spinal cord where they can wreak havoc on nerve fibers and their insulation. Monoclonal antibodies are produced in a lab, and act like our own antibodies, attacking foreign substances in the body. This is the first time an anticlonal antibody has been approved as a therapy for MS.
It's believed MS is an autoimmune disease, in which the immune system goes awry, attacking nerve fibers and a fatty substance that protects them known as myelin (MYE-uh-lin). When myelin is stripped away, inflammation results, as well as symptoms like blurred vision or numbness.1
Expedited Clinical Trial Review
The Food and Drug Administration granted the approval following an accelerated review process that included 1-year data from two ongoing Phase III studies: the AFFIRM monotherapy trial and the SENTINEL add-on trial with interferon beta-1a (Avonex). The AFFIRM study includes 942 people newly diagnosed with MS who were chosen at random to receive either a 300 milligram dose of Tysabri intravenously or placebo once every 4 weeks. Investigators found that the medication lowered the rate of relapses by two-thirds compared to those taking placebo after one year.
Moreover, 60 percent of patients taking Tysabri developed no new or newly enlarging brain lesions compared to 22 percent of those taking placebo. Seventy-six percent of the patients in the Tysabri group remained relapse free during the 1-year period, while 53 percent of those taking placebo did so.
Difficult-to-Treat Patients
The SENTINEL trial involves 1,171 patients who continued to experience MS symptoms after taking interferon beta-1a. Of those, 589 were randomly assigned to receive Tysabri versus 582 who are receiving placebo, both of those added to the current interferon beta-1a treatment schedule.
Of those who added Tysabri to their interferon therapy, 54 percent reduced their risk of relapse compared to the effect of interferon beta-1a alone, the researchers reported. The annual relapse rate was 0.36 for those receiving Tysabri added to interferon beta-1a versus 0.78 with interferon plus placebo.
On MRI scans, the researchers found that 67 percent of those taking the Tysabri/Avonex combination had no new or newly enlarging brain lesions, compared to 40 percent of those taking Avonex alone. Two-thirds in the Tysabri group remained relapse-free during the 1-year period, compared to 46 percent of those on placebo.
"Patients who have discontinued therapy, are newly diagnosed with MS, or have persistent active disease despite being on a current therapy will benefit from Tysabri," said Richard Rudick, MD, lead investigator in the SENTINEL trial, and director of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic Foundation.
Final results of the 2-year trials are expected in the first half of 2005. Patients who complete the trials will be eligible to enroll in a long-term safety extension study, according to Biogen Idec.
The most frequent side effects were headache, fatigue, urinary tract infection, depression, lower respiratory tract infection, joint pain and abdominal discomfort.
1. National Multiple Sclerosis Society. What is Multiple Sclerosis?
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
