Sept. 13, 2006 — Patients with relapsing multiple sclerosis responded well to the experimental drug fingolimod, giving new hope for an oral MS drug, new research shows.

The findings are published in the latest New England Journal of Medicine.

If the drug is shown to be both effective and safe in larger and longer studies, it could soon offer MS patients something they have not had in the past — an effective treatment that is taken in pill form, instead of by injection or infusion.

Fingolimod, which is manufactured by Novartis Pharmaceuticals, is one of several experimental, orally delivered drugs that are currently under development for the treatment of multiple sclerosis. Novartis is a WebMD sponsor.

About 2 million people worldwide have MS, which is the leading cause of disease-related neurologic disability among young adults.

Currently available treatments effectively reduce relapse rates in about 30% of patients, but many patients do not stay on the drugs because of adverse reactions and difficult side effects.

“There has been a crying need for better therapies for MS,” National MS Society director of biomedical research Patricia O’Looney, MD, tells WebMD. “These are exciting preliminary findings for an experimental oral therapy for MS, but larger and longer term studies are needed to determine if this drug lives up to its early promise.”

Trapping T Cells

Although the exact cause of MS remains a mystery, most experts now consider it an autoimmune disease. Immune cells are believed to be responsible for the destruction of the protective coating, called myelin, which surrounds the nerves in key areas of the brain and spinal cord.

This destruction hinders the nerves’ ability to send electrical signals, resulting in problems with muscle movement, coordination, balance, and cognition. In its later stages, MS can leave patients paralyzed, but it is not usually fatal.

Out-of-control T cells (a type of immune cell) are thought to attack the myelin, causing the damage, and it is these cells that are targeted by the new therapy.

T cells and other immune cells act like generals in an army, involved in protecting the body. In people with autoimmune diseases, however, these immune cells can become the enemy, attacking various parts of the body.

Fingolimod, also known as FTY720, essentially traps T cells in the lymph nodes, keeping them out of the blood and away from the central nervous system where they do their damage.

In the newly published study, paid for by the drug’s manufacturer, MS patients were treated with one of two fingolimod doses for up to a year.

In the first six months of the study, 255 patients received either a once-a-day oral dose of 1.25 milligrams of fingolimod, 5 milligrams of the drug, or a placebo. During the second six months the remaining patients on a placebo were switched to the active drug.

In the patients switched from a placebo to fingolimod, the relapse rate was reduced by at least 70% during the second six-month study phase, compared with the first six months on a placebo.

The researchers also reported that the number of MS-related brain lesions seen on MRI scans was much lower in the actively treated patients than among those on a placebo.

Among the 227 patients who remained in the trial for a year, brain lesions and relapse rates remained low in the group taking fingolimod the entire time, and lesions and relapse rates decreased with active treatment in the group switched from a placebo.

“Undesired Consequences”

Although fingolimod was well tolerated by most patients, the drug’s long-term safety in the treatment of MS will not be known until studies that include thousands of patients are complete, Harvard University professor of pathology Ulrich von Andrian, MD, tells WebMD.

The most common side effects reported in fingolimod users included shortness of breath, inflammation of the nose and throat, headache, diarrheadiarrhea, and nausea. Fingolimod users also had more cases of elevation in a liver enzyme test. More adverse side effects were noted in the group receiving the higher dose of fingolimod. One case of a serious neurological syndrome was reported in a 52-year-old woman taking the 5-milligram dose for 10 weeks. Although she had improvement of symptoms after the drug was stopped, she had some residual effects after 15 months.

Concerns about the MS drug Tysabri, which acts in a different way to suppress the immune system, led to an FDA warning earlier this year. The drug was temporarily withdrawn from the market early in 2005 after three patients developed a rare and serious brain disease.

In an editorial accompanying the study, von Andrian wrote that long-term suppression of the migration of T cell lymphocytes could have “undesired consequences.”

Enrollment for a worldwide phase III trial of fingolimod to include around 2,000 MS patients, began in June.

Novartis spokeswoman Denise Brashear tells WebMD that if all goes well in the phase III studies, the company hopes to petition the FDA by 2009 to approve the drug for sale in the U.S.

By Salynn Boyles
WebMD Medical News
September 13, 2006

SOURCES: Kappos, L. New England Journal of Medicine, Sept. 14, 2006; vol 355: pp 1124-1140. Ludwig Kappos, MD, department of neurology and research, University Hospital, Basal, Switzerland. Ulrich von Andrian, department of pathology, Harvard Medical School, Boston. Patricia O’Looney, MD, director, biomedical research, National Multiple Sclerosis Society, New York City. WebMD Medical News: “FDA Panel: Bring Back Risky MS Drug.” Demise Brashear, spokeswoman, Novartis Pharmaceuticals Corporation, East Hanover, N.J.