Trial shows Daclizumab therapy improves multiple sclerosis outcome

May 24 2004

A small clinical trial of patients with multiple sclerosis (MS) who did not respond to interferon alone found that adding the human antibody daclizumab improved patient outcome. Patients who received the combined therapy had a 78 percent reduction in new brain lesions and a 70 percent reduction in total lesions, along with other significant clinical improvements. The trial was led by investigators at the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health. Findings will appear in the Early Edition of the Proceedings of the National Academy of Sciences the week of May 24-28, 2004.¹

MS is a chronic disease marked by inflammation in the central nervous system and development of lesions in the brain. Messages from the brain to the body are interrupted as nerve fibers begin to lose their protective coating of myelin, resulting in muscle weakness, problems with vision and coordination, pain, and, in some patients, cognitive impairments. Approximately 250,000 to 350,000 people in the United States suffer from MS and about 200 new cases are diagnosed by physicians each week. There is no cure for the disorder.

NINDS investigator Roland Martin, M.D., and colleagues studied 11 patients with either relapsing-remitting² or secondary progressive³ MS. Each patient was treated with beta interferon – a naturally occurring antiviral protein commonly used to treat MS. Patients also received 7 treatments of daclizumab (a genetically engineered human antibody that blocks the interleukin-2 receptor on immune cells) administered intravenously at 2-week, and later, 4-week intervals.

Ten patients showed a dramatic reduction in both the severity and number of brain lesions as demonstrated by magnetic resonance imaging. The decrease in new lesions, as well as the total decrease in lesions, occurred gradually over a 2-month span. Improvement was also seen on a neurological rating scale and in a test of hand function. The clinical improvement was unexpected in such a small trial, since a larger number of patients is usually required to show clinical effects. One patient with extremely high inflammation activity responded initially to daclizumab but, as disease activity returned, was given higher doses of the antibody and was excluded from final analysis.

"There is great interest now in new approaches and new therapies for a disorder about which we know too little and have only moderately effective therapies," said Dr. Martin. "The combined therapy was well tolerated by all patients, with side effects that were either mild or clearly not caused by daclizumab." He said the therapy limits the activity of T-cells that attack the myelin coating around the nerves, without shutting down the entire immune system.

"While these results are preliminary, this discovery offers hope for thousands of patients with certain forms of MS. Findings like this are helping us to better understand how this disease affects the immune system, which offers hope for all MS patients," said Story C. Landis, Ph.D., NINDS director.

Further studies are needed to confirm the extent of the clinical benefit of daclizumab on typical MS patients and whether daclizumab is similarly effective as a stand-alone therapy.

The study was a collaboration between the NINDS and its sister agency, the National Cancer Institute (NCI). Thomas Waldmann, M.D., chief of the metabolism branch for NCI's Center for Cancer Research, developed the antibody used in the trial.

Daclizumab (trade name Zenapax®) received FDA approval in 1997 for use in kidney transplantation.

The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation's primary supporter of biomedical research on the brain and nervous system.

¹Bielekova B, Richert N, Howard T, Blevins G, Markovic-Plese S, McCartin J, Wirfel J, Ohayon J, Waldmann TA, McFarland HF, and Martin R. "Humanized Anti-CD25 (Daclizumab) Inhibits Disease Activity in Multiple Sclerosis Patients Failing to Respond to Interferon-beta." Proceedings of the National Academy of Sciences, Vol. 101, Issue 23, pp. 8705-8708.

²A course of MS in which some patients experience a series of attacks followed by complete or partial remission of symptoms that return after a period of stability.

³MS that may begin with a relapsing-remitting course, followed by gradual clinical decline with no distinct remissions.

Originally prepared by Paul Girolami, NINDS Office of Communications and Public Liaison. http://www.ninds.nih.gov