Questions And Answers About Tysabri (Natalizumab)
Q. What is Tysabri (pronounced tie-SAB-bree)?
A. Tysabri (whose scientific name is natalizumab, pronounced: nat-tal-IZ-zue-mab) is a laboratory-produced monoclonal antibody. It was formerly called Antegren. It has been recently approved for marketing by the U.S. FDA for relapsing forms of MS, based on data from the first year of two, 2-year clinical trials. Tysabri is designed to hamper the movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier,” and into the brain and spinal cord. The drug inhibits this movement by attaching to alpha 4-integrin, a protein on the surface of immune T cells that normally enables them to adhere to and pass through the blood-brain barrier. Because of this mode of action, Tysabri is called a selective adhesion molecule inhibitor (or “SAM”).
Q: How is Tysabri different from the other approved therapies?
A. Unlike other approved therapies for MS (Betaseron, Copaxone, Avonex, Rebif and Novantrone), Tysabri is an agent designed specifically to impede the movement of immune T cells into the blood-brain barrier. Although the interferon betas (Betaseron, Avonex, Rebif) also influence the movement of immune cells through the blood-brain barrier, they have many other influences on immune function in persons with MS.
Q: Who should take Tysabri?
A. Tysabri has been approved for persons with relapsing forms of multiple sclerosis. That includes anyone whose MS undergoes waxing and waning of symptoms. Relapsing forms of MS may include those with relapsing-remitting MS, progressive-relapsing MS, and those with secondary-progressive MS who experience relapses.
Q: What are the most commonly reported side effects of Tysabri?
A. Results available from the first year of clinical trials indicate that the most common side effects included headache, fatigue urinary tract infection, depression, lower respiratory tract infection, joint pain and abdominal discomfort. The overall incidence of infection was similar between those on Tysabri and those on placebo. Serious infections such as bacterial pneumonia and urinary tract infections occurred in 1.3 percent of placebo-treated patients and 2.1 percent of Tysabri-treated patients. Tysabri has been associated with hypersensitivity reactions, including serious systemic reactions, which occurred at an incidence of less than 1 percent of patients. Longer term safety information is not available.
Q: What did the clinical trials show about Tysabri’s effectiveness?
A. First-Year Results from AFFIRM Study: The AFFIRM study of Tysabri alone is a placebo-controlled study involving 942 participants worldwide. Participants were randomly assigned to receive either 300 mg IV infusion of Tysabri or inactive placebo every four weeks. Those on active therapy showed a statistically significant, 66% reduction in relapse rate. The annual rate of relapses in the Tysabri group was 0.25 versus 0.74 in the placebo group.
The secondary outcomes for the study were also significantly different for the treatment versus placebo groups. Sixty percent of those on Tysabri developed either no new MRI lesions or no newly enlarging lesions (patches of disease activity), compared to 22 percent of the placebo group. MRI scans taken after the first full year of treatment showed that 96 percent of actively treated participants had no gadolinium-enhancing lesions (lesions that show active inflammation) versus 68 percent of the placebo group. The proportion of participants who remained relapse-free was 76 percent of the treatment group versus 53 percent of the placebo group, which was also statistically significant.
First-Year Results from SENTINEL Study: The SENTINEL study of Tysabri added to Avonex, compared with a placebo plus Avonex, involves 1,171 participants worldwide. For this trial, individuals using Avonex who continued to experience disease activity were randomly assigned to add Tysabri or placebo to their standard Avonex therapy.
The participants who had Tysabri added to Avonex experienced a 54 percent reduction in the rate of clinical relapses compared to those on placebo and Avonex. The annual rate of relapses in the Tysabri plus Avonex group was 0.36, versus 0.78 in the placebo plus Avonex group. MRI scans taken after the first full year of treatment showed that 96 percent of the Tysabri plus Avonex group had no gadolinium-enhancing lesions versus 76 percent of the placebo plus Avonex group. The proportion of participants who remained relapse-free was 67 percent in the Tysabri plus Avonex group, versus 46 percent in the placebo plus Avonex group.
The secondary outcomes for this study were also significantly different for the treatment versus placebo groups. Sixty-seven percent of those in the treatment group developed no new or no newly enlarging MRI lesions, compared to 40 percent of the placebo plus Avonex group.
Because the companies submitted an application to the FDA about halfway through the two-year clinical trials, the one-year data are informative but incomplete; the complete set of results from these studies are not yet available.
Q: How is Tysabri taken?
A. Tysabri is given by infusion into a vein every 4 weeks. This can be done in a doctor’s office, clinic or hospital out-patient station.
Q: How long does an infusion take?
A. About one hour.
Q: Are infusions painful?
A. A person getting an intravenous infusion will probably feel a sharp pain or some discomfort when the needle penetrates the skin and vein, but then the discomfort should subside as the infusion proceeds. There may also be discomfort when the infusion needle is removed and the site may or may not feel sore for a day or so.
Q: How long can a person take Tysabri?
A. It is not known how long Tysabri needs to be taken, or if there are any longer-term limitations on its use. The drug was approved by the FDA based on only one year’s duration of treatment. Further, post-marketing monitoring of safety will be undertaken to detect any unforeseen adverse events that may occur in persons taking the drug for longer periods.
Q: How much does Tysabri cost?
A. The wholesale price of Tysabri has been announced to be $1,808 per vial or dose, which would be $23,504 per year if taken every four weeks. By comparison, the average annual wholesale price of some other MS disease-modifying drugs include: $16,608 (Avonex), $20,553 (Rebif), $16,026 (Copaxone), and $17,827 (Betaseron).
Q: Will this medication be covered by Medicare?
A. At this point, Medicare tends to cover medications that are provided in a physician’s office, which should include Tysabri when delivered under a physician’s care. Specific details about Medicare coverage for Tysabri, however, have not yet been determined.
Q: Will my health insurance cover the cost of Tysabri infusions?
A. Each health plan determines its own coverage. In the past, new MS medications have seen relatively rapid acceptance for prescription coverage costs when such are in place. Individuals may consult with their physicians and health plans for more information.
Q: Should I switch from the disease-modifying therapy I’m taking now?
A. There is no direct information that indicates whether individuals who are using existing disease-modifying therapies should switch to Tysabri. This question is something that can only be answered through discussions between an individual and his or her neurologist. There is currently no available information about the relative benefits or safety of Tysabri in comparison with any other currently available treatments for MS.
Q: Where can I call to get more information about Tysabri?
A. Biogen Idec and Elan have established a toll-free number to help answer questions: 1-800-456-2255; they have also established a Web site at: www.tysabri.com
You may also contact the National MS Society at 1-800-FIGHT MS and check our Website for further updates.