09/19/2012 05:48 EDT | Updated 11/19/2012 05:12 EST

Oral drug shows promise for relapsing-remitting MS, studies find

TORONTO - Two major patient trials of an experimental drug for the relapsing-remitting form of multiple sclerosis have found the oral medication significantly improves patients' symptoms.

The studies, both published in Wednesday's issue of the New England Journal of Medicine, show the drug BG-12 reduces the rate of annual relapses and the number of brain lesions that are hallmarks of the disease.

The studies show BG-12 (dimethyl fumarate), a drug long used in Europe to treat psoriasis, cut the annualized rate of relapses among MS patients participating in the studies by 45 to 50 per cent compared to MS patients given a placebo.

"That is a very robust reduction in relapses," said Dr. Robert Fox, director of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio and principal investigator of one of the studies, known as CONFIRM.

"It's not a cure. None of our therapies is a cure for MS at this point. But it appears to be a greater reduction than what we see with injectable therapies, which (offer) roughly a 30 per cent reduction in the annualized relapse rate."

Fox said patients in the CONFIRM and DEFINE studies who were randomly assigned to receive BG-12 also had considerable reductions in brain lesions — between 70 and 90 per cent lower than patients given the dummy pill, depending on the type of brain lesion looked at in MRI exams.

Both studies showed a slowing of the progression of MS-related disability, although only the DEFINE study conducted by European researchers had results considered statistically significant, Fox said Wednesday from Paris, where he was attending a medical meeting.

BG-12 was well-tolerated for the most part, although some patients experienced flushing of the skin on the chest, neck and face within about 45 minutes of taking the pill, an effect that resolved within 15 to 20 minutes, he said.

More troublesome for patients was gastrointestinal upset, including nausea, vomiting and diarrhea, associated with the drug. Fox said those adverse symptoms seem to peak in the first month after starting the drug and decline in frequency and severity as time goes on.

BG-12, developed by Biogen Idec Inc., must be approved by government regulatory bodies such as the U.S. Food and Drug Administration and Health Canada, before it would become available to treat patients.

"What this drug appears to provide is a significant step forward in the combination of efficacy, safety and tolerability," said Fox.

"So it appears to be more effective than our standard first-line injectable therapies."

Multiple sclerosis is a disabling disease in which the protective coating around nerve cells, called myelin, is attacked by the immune system and progressively destroyed. With an estimated 55,000 to 75,000 Canadians affected, Canada has one of the highest rates of MS in the world.

There are a number of forms of the disease, including primary- and secondary-progressive, for which there are no effective treatments.

A number of injectable medications for relapsing-remitting MS are prescribed by doctors in Canada, among them interferon-beta, Copaxone and Tysabri.

Dr. Paul O'Connor, director of the multiple sclerosis clinic and MS research at St. Michael's Hospital in Toronto, agreed the efficacy and safety of BG-12 "look pretty good."

O'Connor, who was not involved in either study, said that if approved, BG-12 would be "another tool in the toolbox" for doctors to prescribe to patients with relapsing-remitting MS.

In Canada, the only oral drug approved for widespread use in Canada to date is Gilenya (fingolimod), which has been associated with heart-rate and heart-rhythm irregularities in some patients.

Aubagio (teriflunomide) was recently approved by the FDA, following multi-centre clinical trials led by O'Connor, and is in the regulatory pipeline in Canada, as is BG-12.

"It's good for MS patients because they could have in Canada within a year maybe three oral options," O'Connor said.

As to which one is best, that could only be determined by comparing the three drugs in a patient trial, he said.

"Until you have a head-to-head study, you don't know."

Fox said that although not perfect, BG-12 could offer an alternative for patients who have difficulty with shots or who don't respond sufficiently to the injectable treatments.

If approved, BG-12 might also be an option for people prescribed Tysabri, which is a highly effective medication but carries the risk of a brain infection called PML (progressive multifocal leukoencephalopathy) with continued use, he said.

In an NEJM editorial accompanying the studies, neurologist Dr. Alan Ropper of Brigham and Women's Hospital in Boston writes that "the question of switching from an existing medication to an oral agent in a patient with relapses, or even in a patient with few relapses but for whom a new drug is more convenient, is a difficult and unresolved one."

"It is not clear at the moment how to advise patients about the new oral drugs, but the overall benefit-to-risk assessment, as of this month, may favour fumarate."