(Buffalo, NY - September 25, 2000) -- Early treatment with the multiple sclerosis (MS) therapy interferon beta-1a, or Avonex®, can significantly reduce the rate at which individuals at high risk for the disease actually develop clinically definite multiple sclerosis (CDMS), according to a new study published this week in the New England Journal of Medicine.

The first indication that a patient may have MS is a single, clinical, demyelinating event of the optic nerve, spinal cord, or brain stem. A clinically definite case of MS is not considered until a patient has had a second demyelinating event, separated by time and location in the central nervous system. To date, there are no well-accepted guidelines for the treatment of these patients, who are at high risk for, but have not yet developed, clinically definite MS.

This trial – known as the CHAMPS study -- sought to determine the effect of treatment with Avonex, already proven beneficial to patients diagnosed with MS, in individuals who had experienced a single demyelinating event and whose magnetic resonance imaging (MRI) scans showed brain abnormalities indicating that they were at high risk of developing CDMS.

“The results of this study demonstrated that treatment with interferon beta-1a, or Avonex, reduced the rate of development of clinically definite MS for these high-risk individuals by 44 percent versus treatment with placebo,” said principal investigator Lawrence Jacobs, M.D, Head of the Department of Neurology at the Buffalo General Hospital, Chief of the Baird Multiple Sclerosis Research Center at Millard Fillmore Hospital, and Irvin and Rosemary Smith Professor of Neurology at the State University of New York at Buffalo. “Avonex also showed a highly significant positive impact in reducing the rate at which patients developed brain abnormalities, or lesions, visible on MRI scans.”

The CHAMPS study was a randomized, double blind, placebo–controlled, Phase III clinical trial involving 383 patients determined to have a high probability of developing CDMS based on brain MRI changes and clinical events consistent with MS. Participants received weekly intramuscular injections of either 30 mcg of Avonex (Interferon beta-1a) or placebo. The study was conducted at 50 clinical centers in the USA and Canada. The trial was planned to last three years but was stopped early following a preplanned interim efficacy analysis indicating positive results.

The primary study outcome was the development of CDMS, which was defined as the occurrence of either 1) a new visual/neurological event or 2) progressive neurological deterioration. Brain MRI results served as a secondary outcome.

According to Dr. Jacobs, the study yielded the following results:

1. The rate of development of CDMS was 44 percent lower in the Avonex-treated group than in the placebo-treated group.

2. The increase in brain MRI T2 lesion volume was 91 percent lower in the Avonex-treated group than in the placebo-treated group.

3. With the results of this study showing a strong benefit of Avonex treatment at the time of the first clinical event, there is added justification for obtaining brain MRIs at the earliest symptoms of MS. Previously, MRIs were considered useful in predicting the possibility of developing CDMS but were not considered necessary because they would not affect treatment and patient management.

Over 200 new cases of multiple sclerosis are diagnosed each week in the United States alone. Many more individuals are at risk of developing the disease, which is the most common neurological disorder affecting young people in this country.

“To date, there are no accepted guidelines for treating patients who have experienced a single MS-like attack but who have not yet developed clinically definite MS,” Dr. Jacobs said. “This study is extremely important because it indicates that initiating therapy with Avonex at the first indication that a patient may have MS can significantly delay the development of the disease.”

Avonex was approved by the FDA in 1996 and is demonstrated to have beneficial effects when used to treat patients with relapsing forms of MS, including slowing the accumulation of physical disability and decreasing the frequency of clinical exacerbations.

“Avonex is the only MS therapy available that is proven to reduce the rate at which high-risk individuals develop clinically definite multiple sclerosis,” said Dr. Jacobs. “In addition to its previously demonstrated benefits, our results show that initiating once-weekly intramuscular injections of 30 mcg of Avonex, the currently approved dose, beginning at the time of a first MS attack, is beneficial in patients who have brain MRI evidence of prior demyelination.”

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects approximately 350,000 Americans and about one million individuals worldwide. It is a disease of young adults, mostly women, with onset typically between 20 and 40 years of age. Symptoms of MS may include vision problems, loss of balance, numbness, difficulty walking and paralysis.

The disease is believed to be caused by the destruction of myelin by the immune system. Myelin is the fatty tissue that surrounds and protects central nervous system nerve fibers and facilitates the flow of nerve impulses to and from the brain. The loss of myelin disrupts the conduction of nerve impulses, producing the symptoms of MS.

STUDY PROFILE: The effect of intramuscular Interferon beta-1a treatment initiated at the time of a first acute demyelinating event on the rate of development of clinically definite multiple sclerosis.

Co-authors: Lawrence D. Jacobs, M.D., Department of Neurology, Buffalo General Hospital, Buffalo, NY; Roy W. Beck, MD. Ph.D., the Jaeb Center for Health Research, Tampa, FL; Jack H. Simon, Ph.D., the University of Colorado Health Sciences Center, Denver, CO; R. Phillip Kinkel, M.D., The Mellen Center for MS Treatment and Research, The Cleveland Clinic Foundation, Cleveland, OH; Carol M. Brownscheidle, Ph.D., Department of Neurology, Buffalo General Hospital, Buffalo, NY; Thomas J. Murray, M.D., MS Research Unit, Centre for Clinical Research, Victoria General Hospital Site, QE II Health Sciences Centre, Halifax, NS; Nancy A. Simionian, M.D., Biogen, Inc., Cambridge, MA; Peter J. Slasor, Sc.D., Biogen, Inc., Cambridge, MA; Alfred W. Sandrock, M.D., PhD., Biogen, Inc., Cambridge, MA; and the CHAMPS Study Group.

Method: 383 patients with the onset of a first acute demyelinating event (optic neuritis, incomplete transverse myelitis, or brainstem/cerebellar syndrome) and with brain MRI evidence of prior subclinical demyelination were assigned to receive weekly intramuscular injections of 30 mcg of interferon beta-1a (AVONEX®) (N=193) or placebo (N=109). The study outcomes were 1) the development of clinically definite MS and 2) brain MRI changes. The trial was stopped following a preplanned interim efficacy analysis.

The cumulative probability of the development of clinically definite MS over the three-year follow-up period was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio = 0.56, 95 percent confidence interval = 0.38 to 0.81, P=0.002). The benefit of treatment was also seen as a relative reduction in brain MRI T2 lesion volume progression, number of new or enlarging T2 lesions, and number and volume of new enhancing lesions (P<0.001 for each at 18 months).

More information on the CHAMPS study, including web cast interviews, can be found at http://www.understandingms.com