Mitroxantrone, approved in 2000, is a chemotherapeutic drug that suppresses the immune system and can lead to leukemia or heart damage.
Natalizumab (Tysabri), which received accelerated FDA approval in 2004 and is considered the most effective drug available today, was taken off the market in February 2005 after three patients in clinical trials developed progressive multifocal leukoencephalopathy, a fatal viral disease. After an FDA review, it has been available under a special program in which patients are closely monitored for opportunistic infections.
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On the horizon
There's clearly a lot of room for improvement, which is one reason why doctors are excited about options on the horizon.
Fingolimod, originally developed to prevent organ rejection in transplant patients, blocks a signal that allows T-cell lymphocytes to cross into the brain. At the American Academy of Neurology meeting this year, researchers reported that 173 patients with a relapsing form of MS showed a decline in the relapse rate over 36 months from 0.31 relapses per year to 0.20, a 30% decrease in their relapse rate when they took fingolimod. In just six months, the number of patients with brain lesions decreased from an average of 2.2 per patient when taking the placebo down to 1.29. In addition, after 36 months, brain scans revealed that 89% of patients had no evidence of inflammation.
Fingolimod is promising not only for effectiveness but because it comes in pill form, Centonze says. "For patients that must receive injections every other day or every single day, the quality of life is really affected. Taking pills can change this."
Another compound on the horizon is alemtuzumab (Campath), a monoclonal antibody designed and FDA-approved for fighting leukemia. In a trial of 334 patients published in October in the New England Journal of Medicine, researchers reported that the drug could reduce the relapse rate in early-stage MS patients by two-thirds relative to the standard MS drug interferon beta-1a.
UCSF's Green says the findings are impressive because this is the first MS trial to compare a new drug to an approved compound rather than a placebo and yet "it still had a remarkable effect on reducing disease activity."
Rituximab, an antibody that was designed for treating rheumatoid arthritis, is also being studied, in a clinical trial headquartered at UCSF. Rituximab is directed at the immune system's B cells, rather than T cells that have been targeted by MS researchers since the 1970s.
