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Analysis Shows Tysabri Helps Reduce Vision Loss in Relapsing MS

April 20, 2007

In the first large-scale validation of a new method for evaluating visual function in multiple sclerosis, analysis of data from two pivotal clinical trials of Tysabri®(natalizumab, Biogen Idec and Elan) showed that the drug can reduce vision loss in relapsing multiple sclerosis. The method, called “low-contrast letter acuity,” has been under investigation by lead author Laura Balcer, MD, MSCE, with co-funding from the National MS Society. The study was published in the April 17, 2007 issue ofNeurology(2007;68:1299-1304).

Background:Visual impairment is common in MS. Dr. Balcer has been investigating the use of a low-contrast eye test (gray letters against a white background) to evaluate visual impairment in MS. The gray letters can generally be read by people with normal eyesight, but scores for these tests have been shown to be significantly lower in individuals with MS. Low-contrast letter acuity can pick up abnormalities even when high contrast tests (e.g., the typical eye chart with black letters on a white background) do not.

Tysabri was approved by the FDA for relapsing MS based on its ability to slow disability progression and reduce relapses in two pivotal clinical trials, called AFFIRM (which compared Tysabri alone to inactive placebo in 942 people with relapsing MS) and SENTINEL (which tested Tysabri plus interferon beta-1a or Tysabri plus placebo in 1171 people with relapsing MS). (Details of these trials are summarized below.)

Results of the Study:

Built into both trials were periodic measurements of participants’ eyesight using the low-contrast letter acuity eye charts. Data were collected on the low-contrast eye tests given every 12 weeks.

The data analysis, now being published for the first time, indicated that Tysabri reduced loss of visual function, preventing worsening of vision scores and significantly reducing the risk of vision loss. For the AFFIRM trial, the risk of vision loss (defined as a worsening in score by two rows of letters on the eye chart) using the lowest contrast level was reduced by 35% in those on Tysabri versus placebo, and in the SENTINEL trial by 28%.

These results suggest that Tysabri can prevent worsening of visual function in relapsing MS and reduce the likelihood of sustained loss of visual function due to inflammatory destruction of myelin on the nerve fibers that connect the eyes and the brain.

The findings also show that low-contrast letter acuity testing provides a more sensitive method to evaluate visual function in MS clinical trials than was previously available. In addition, testing with low-contrast letter acuity is relatively simple, quick, and inexpensive.

Background on the Clinical Trials:

In a two-year clinical trial (the AFFIRM study) of Tysabri alone, 942 individuals received either Tysabri or inactive placebo every four weeks for more than two years. The treated group experienced a 42% reduced risk of progression of disability, a 68% reduction of clinical relapses, and an 83% reduction in the development of new or newly enlarging MRI-detected brain lesions. Tysabri also reduced the mean number of enhancing (active) MRI lesions by 92% after the first and second year. (The New England Journal of Medicine2006;354:899-910 ).

A second two-year trial (the SENTINEL study) involved 1171 individuals with relapsing MS who were on Avonex®(interferon beta-1a, Biogen Idec) but had experienced at least one relapse during the previous 12 months. All participants continued on Avonex, in combination with either Tysabri or inactive placebo given by intravenous infusions every four weeks for up to 116 weeks. After one year, 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, which was also maintained at two years with a 55 percent reduction.

This combination therapy resulted in a 24 percent decrease in the risk of sustained disability progression. MRI scans showed an 83-percent reduction in the Tysabri plus Avonex group in enlarging MRI lesions, and an 89-percent reduction in lesions showing active inflammation. (The New England Journal of Medicine2006;354:911-923). Two cases of PML (progressive multifocal leukoencephalopathy, a rare and frequently fatal disease of the central nervous system) were diagnosed in those on combination therapy. One of those cases was fatal. A third case of PML, also fatal, was uncovered in another person who had taken Tysabri during a clinical trial for Crohn’s disease.

For more information on Tysabri,

-- Research and Clinical Programs Department

Tysabri is a registered trademark of Biogen Idec and Elan.

Avonex is a registered trademark of Biogen Idec.

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