March 1, 2006
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
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
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
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.