Oral MS drug passes tests

BG-12 suppresses relapses

People with multiple sclerosis might soon have a new option for controlling their disease with pills instead of shots. Two studies in the Sept. 20 New England Journal of Medicine demonstrate that a variation on a drug used against psoriasis for years in Germany holds off MS relapses and has minimal side effects.

“These data look good. Both studies show a reduction in relapses with really pretty robust effects,” says Clyde Markowitz, a neurologist at the University of Pennsylvania who wasn’t involved with the trials.

The drug, called BG-12, has been submitted to the U.S. Food and Drug Administration for approval by the biotech company Biogen Idec. Markowitz expects it to get approved. “It would be a clear benefit to the MS population to have another option,” he says. If approved, BG-12 would be the third oral drug available to treat MS.

The disease results when the immune system attacks the fatty myelin sheaths coating nerves in the central nervous system, leading to impaired muscle control, balance, vision and speech. BG-12, or dimethyl fumarate, has anti-inflammatory, cell-protective and antioxidant effects, which earlier work suggested could suppress the aberrant immune reactions in MS patients.

Scientists in both studies recruited MS patients and randomly assigned some in each group to BG-12 or placebo tablets. In one of the studies, an additional group was randomly assigned to get an injectable MS drug called glatiramer acetate (Copaxone). In other respects the studies were nearly identical, each enrolling more than 1,000 MS patients, ages 18 to 55, in 28 countries apiece, for two years of treatment. Both trials included a mix of North American and European researchers.

On average, patients getting BG-12 went from 72 weeks to more than 90 weeks before experiencing a relapse, compared with 30 and 38 weeks among those assigned a placebo in the two studies. Magnetic resonance imaging also revealed strikingly fewer lesions in the brains of patients after two years of BG-12 than in those on placebos.

The results come at a heady time in MS research, with several drugs in testing and some newly approved in the past decade. The most recent was the oral drug teriflunomide (Aubagio), which the FDA cleared on September 12. It joins another oral drug, fingolimod (Gilenya), which was approved in 2010. Two injectable cancer drugs have also shown promise against MS (SN: 2/23/08, p. 125; SN: 11/22/08, p.9), and these or similar versions of them are awaiting FDA approval as MS drugs. For years, the standard treatment has been injectable anti-inflammatory interferon beta.

The oral drugs are more convenient to use than interferon and the other injectables, boosting patient compliance, says Robert Fox, a neurologist at the Cleveland Clinic who coauthored one of the studies. The oral drugs also seem more effective at preventing relapses than the injectables, with the exception of a potent injectable called natalizumab (Tysabri), which was first approved in 2004. But natalizumab stumbled on early reports of side effects and was pulled off shelves temporarily. It’s been back on the market for six years, with label warnings (SN: 3/4/06, p. 131).

It may take years before any of the oral drugs proves better overall than the others. “It is not clear at the moment how to advise patients about the new oral drugs, but the overall benefits-to-risk assessment, as of this month, may favor fumarate,” meaning BG-12, says physician Allan Ropper of Brigham and Women’s Hospital in Boston, writing in the same New England Journal of Medicine issue. “The two-decade safety record of fumarate in psoriasis lessens concern about long-term risk,” he says.

Markowitz says that advances in understanding the immune system are driving the progress against MS. “If you can modulate immune functions, you can control disease activity,” he says.

While the spate of new drugs has given patients and doctors more options, it also has made it more difficult to test drugs. “With those other therapies [available], it’s a lot harder to keep patients — from an ethical point of view — on a placebo for two years,” Fox says.

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