Tysabri effective for MS but carries some risk

By Karla Gale

NEW YORK (Reuters Health) - Tysabri, a drug made by Biogen Idec and Elan Pharmaceuticals, significantly reduces the rate of disease progression in patients with relapsing multiple sclerosis (MS), according to the results of two trials reported in this week's New England Journal of Medicine.

"The available drugs for MS, interferon and Copaxone, have been shown in trials to reduce relapse rate by one third," Dr. Richard A. Rudick, of the Cleveland Clinic Foundation in Ohio, told Reuters Health. The two current trials show that "the effectiveness of Tysabri was very excellent," far better than that of the other available drugs.

However, a review of more than 3000 patients treated with Tysabri (which is known as natalizumab, generically) in clinical trials revealed that the drug is associated with a small risk of a serious neurological disease called progressive multifocal leukoencephalopathy or PML.

Tysabri was approved by the US Food and Drug Administration in November 2004 for the treatment of MS, but it was suspended in February 2005 after PML cases were reported.

In one of the new studies, Dr. Chris H. Polman, from the VU Medical Center in Amsterdam, and his team recruited 942 patients with relapsing remitting MS, who were randomly assigned to receive natalizumab every 4 weeks or an inactive placebo injection.

After 2 years of treatment, compared with placebo, natalizumab was associated with a 42 percent decrease in the risk of a sustained progression of disability and 59 percent reduction in the risk of relapse. The active treatment also reduced the number of new or enlarging MS lesions in the brain by 83 percent.

In the second trial, Dr. Rudick and his colleagues enrolled 1171 MS patients who had at least one relapse during a 12-month period while they were being treated with interferon. Patients were randomly assigned to natalizumab every 4 weeks or placebo while continuing on interferon.

Combined treatment over 2 years resulted in a 24 percent decrease in the risk of sustained disability progression, a 55 percent reduction in rate of relapse, and an 83 percent reduction in new or enlarging lesions, compared with interferon alone.

After the three original cases of PML were reported in patients being treated with natalizumab, Dr. Eugene O. Major, from the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, and colleagues established an independent committee to evaluate suspected cases of PML in 3417 patients exposed to natalizumab in recent clinical trials.

Forty-four patients with possible PML were referred to the committee. PML was ruled out in 43, and 1 case was classified as indeterminate. The three previously reported cases did seem to be actual PML.

When the FDA suspended Tysabri, "patients were devastated," Rudick said. "Imagine being 1 of 7000 patients for whom current therapies are of little benefit and starting a new drug that is known to be a significant advance, then having it suspended abruptly because of this question about safety. We had patients crying in our offices."

He hopes that the FDA will again approve natalizumab under careful conditions for patients "who really need it," with close monitoring so that the early symptoms of PML could be recognized and the Tysabri stopped.

If Tysabri does become available again, Dr. Rudick added, "the decision to use it should be made by the doctor and the patient together. The doctor's job is going to be to decide whether it's a necessary option, and if so, to be sure it's given and monitored properly. Patients should be fully informed so they can make the decision to take on a risk of that magnitude."

Meanwhile, Elan Corporation said on Tuesday it agreed to suspend trading in its shares during the upcoming FDA review of Tysabri, for two days beginning March 7 before the opening bell in New York coinciding with a 1300 GMT suspension on the London and Irish Stock Exchanges.

The company will request that all stock exchanges resume trading at the end of the FDA's Advisory Committee meeting to review the product.

SOURCE: New England Journal of Medicine, March 2, 2006.