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New Oral MS Drugs May Be on the Horizon

Studies Show Cladribine and Fingolimod Are Effective Treatments for Multiple Sclerosis

By Kathleen Doheny
WebMD Health News

Reviewed By Louise Chang, MD

Jan. 20, 2010 -- Two new drugs for multiple sclerosis, both taken orally, reduce the rates of relapses in multiple sclerosis patients -- sometimes keeping 80% or more of patients relapse-free during the study period -- according to new research. The new drugs, if approved, promise an end to injections for some patients.

Results of three studies looking at cladribine and fingolimod for the form of MS known as relapsing-remitting are published online in the New England Journal of Medicine. In an accompanying editorial, a doctor suggests the new drugs could provide a ''new horizon'' for patients and a welcome increase in treatment options.

"These results are big in that first of all, both these therapies look to be very effective, appear to be well tolerated, and they have a novel mechanism of action," says Jeffrey A. Cohen, MD, director of experimental therapeutics at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic and lead researcher of one of the studies.

These two new options may be just the beginning, Cohen tells WebMD. "I think they are harbingers of other medicines on the horizon."

About 400,000 Americans have MS, a chronic, often disabling disease, according to the National Multiple Sclerosis Society. The body turns on itself, attacking myelin, the fatty substance protecting nerve fibers in the central nervous system, leading to damaged nerve fibers and hindering nerve impulses from traveling to and from the brain and spinal cord. That, in turn, produces symptoms such as numbness, limb weakness, and blurred vision. About 85% of MS patients are initially diagnosed with the form of MS known as relapsing-remitting, in which flare-ups are followed by remissions.

The two new drugs would be the first treatment options that don't involve injections or infusions.

Fingolimod for MS

Cohen's team compared fingolimod in two doses -- 1.25 milligrams or 0.5 milligrams -- with an established treatment for MS, intramuscular injection of interferon beta-1a (Avonex) at a dose of 30 micrograms per week.

When the researchers looked at the relapse rate after 12 months in 1,153 patients randomly assigned to one of the three treatment groups, they found that the relapse rate was lower in both groups getting fingolimod.

"The two drugs reduced the relapse rate by 38% to 52%," Cohen tells WebMD. That translates, he says, to a relapse roughly every five or six years instead of every three to four.

While 69% of those treated with interferon beta-1a were relapse-free at a year, nearly 80% of those treated with the higher fingolimod dose were relapse-free and 82.6% of those treated with the lower dose. Those differences between fingolimod doses were small, Cohen says.

In another fingolimod study, researchers compared the drug to placebo, randomly assigning 1,033 patients to either one of two doses of fingolimod (0.5 milligrams or 1.25 milligrams) or to placebo. Patients were followed for 24 months.

Both doses of fingolimod improved the relapse rate. While nearly 75% of those on the higher fingolimod dose were relapse-free during the study, 70.4% of those on the lower dose were, but just 45.6% of those on placebo.

They also measured progression of disability, finding that 88.5% of those on higher doses of fingolimod did not have progression of disability, while 87.5% of those on the lower dose didn't and 81% of those on placebo did not have disability progression.

Cladribine for MS

In a third study, Gavin Giovannoni, MB, PhD, of Barts and the London School of Medicine and Dentistry at Queen Mary University of London and his colleagues evaluated more than 1,300 MS patients who were randomly assigned either two or four short courses of oral cladribine or a placebo. The treatment course included one or two pills a day for four or five days, totaling 8 to 20 days of treatment annually.

Over the nearly two-year study period, nearly 80% of those on the low-dose cladribine were relapse-free, nearly 79% of those on the higher dose were relapse-free, but just 61% of those on placebo were relapse-free.

Giovannoni calls the results excellent. "This means that four out of five people are disease-free in terms of relapses," he tells WebMD.

Cladribine by injection is already approved for treating leukemia under the brand name Leustatin. Shingles occurred in 20 of the patients taking cladribine vs. none in the placebo group.

Other Opinions

"This is really big news," says John Richert, MD, executive vice president for research and clinical programs at the National Multiple Sclerosis Society, New York. MS patients often grow tired of having to have drugs injected, he says, and so stop taking them. "Having oral therapies available increases the likelihood that people will be willing to start the drug early in the course of their disease and continue on the drugs with good compliance long term."

But Richert expressed some caveats about side effects. One side effect of cladribine involves cancer cases. Three cancers occurred in patients in one study getting the low-dose cladribine. "This has to be followed up long term, as the authors note," Richert says.

And, he says, the data on the drugs are confined to the form of MS known as relapsing-remitting. Eventually, some patients with relapsing-remitting make a transition into secondary-progressive MS, in which the disease worsens more steadily. Others have progressive disease from the beginning known as primary-progressive MS, while others have progressive-relapsing MS.

In an accompanying editorial, William Carroll, MD, of Sir Charles Gairdner Hospital in Perth, Australia, calls the new drugs a welcome addition to treatment options but also notes that the existing therapies remain ''very effective, particularly when they are administered early."

He points out that side effects of the new drugs -- including infections, cancers, and low white blood cell counts -- must be weighed against their benefits. Other side effects included herpes zoster (shingles) infections and herpes virus infections; in some cases they were more frequent in those getting the new drugs and in some cases not.

Both drugs work by reducing the number of potentially aggressive lymphocytes, a type of white blood cell, available to enter the central nervous system, although they do so in different ways.

Merck-Serono supported the cladribine study; Novartis Pharma supported the fingolimod studies. Carroll, the editorial author, reports receiving honoraria from Merck-Serono and fees from other pharmaceutical companies. Cohen, who led one fingolimod study, reports receiving consulting fees form Novartis, and Ludwig Kappos, MD, who led the other fingolimod study, has gotten consulting or advisory fees from Novartis and Merck Serono and others. Giovannoni, who led the cladribine study, reports receiving consulting fees from Merck Serono, Novartis, and others.

SOURCES:

John Richert, MD, executive vice president for research and clinical programs, National Multiple Sclerosis Society, New York City.

Jeffrey A. Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis, Cleveland Clinic.

Gavin Giovannoni, MB, PhD, professor of neurology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

Carroll, W. New England Journal of Medicine Online First, Jan. 20, 2010.

Cohen, J. New England Journal of Medicine Online First, Jan. 20, 2010.

Kappos, L. New England Journal of Medicine Online First, Jan. 20, 2010.

Giovannoni, G. New England Journal of Medicine Online First, Jan. 20, 2010.

© 2010 WebMD, LLC. All rights reserved.



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