FDA-approved drug slows progression of multiple sclerosis

Mickie Barg

Last week the FDA approved a drug that aids the crippling secondary-progressive stages of multiple sclerosis.
Mitoxantrone — marketed under the name Novantrone — was previously marketed for use in leukemia treatment and certain types of advanced prostate cancer. Clinical trials in Europe showed a delay in the progression of the disease.
“Our research, by and large, has been focused on (cancer research),” said Mark Gilbert, medical director at Immunex, the makers of Novantrone. “We have not had much experience in neurology until now.”
Multiple sclerosis is a chronic and often debilitating disease of the central nervous system. The patient’s immune system initiates a breakdown of the fatty substance insulating nerve fibers in the brain and spinal cord.
This process causes patches of scar tissue which interfere with the nerve’s ability to transport messages from the brain to other parts of the body.
The drug Novantrone suppresses the activity of the patient’s immune system, consequently slowing down the progression of multiple sclerosis.
Gary Birnbaum, clinical professor of neurology, said the disease patterns change over time. In the beginning there are many attacks and remissions. After a while, though, the secondary progressive stage sets in — flare-ups no longer occur and the disease becomes worse with increased disability.
Symptoms begin with tingling, limb numbness, weakness, impaired vision, loss of balance and muscle coordination, but progress to difficulty walking and, in some cases, paralysis.
“The type and severity of symptoms are variable from person to person — the course of the disease is very unpredictable,” said Virgil Mathiowetz, occupational therapy professor. “Ultimately these symptoms may affect their ability to work, take care of themselves and participate in leisure activities that they enjoy.”
The disease generally strikes people between the ages of 20 to 40, and affects women twice as much as men. It is more prevalent among Caucasians, particularly those of northern European ancestry, than other races. The cause of multiple sclerosis is unknown but geography appears to be a causal factor. Its occurrence in people in the northern states, including Minnesota, is nearly double that of southern states.
There is also evidence, Gilbert said, that where people live during puberty also affects their susceptibility to the disease. If puberty is reached in northern climates, the chance of acquiring the disease increases, regardless of where their adulthood is spent.
“Nobody knows the answer to what causes MS,” said Randall Schapiro, director of the Fairview Multiple Sclerosis Center. “People who get MS are probably genetically susceptible and then something else happens to set it off, like an infection, but we don’t really know.”
About half of the 350,000 people affected with multiple sclerosis in the United States will eventually develop the secondary progressive form of the disease.
At this stage, patients often do not recover from the damage each incident causes. In some cases, the symptoms show up sporadically.
Gilbert said the two clinical trials on Novantrone were conducted in France and 17 other clinical centers in Europe. Although Immunex is based in Seattle, Wash., testing was done in Europe because medical testing for neurological diseases is less conservative than in the United States.
Schapiro explained that since people in the United States are better treated with medications early on in their diagnosis, the opportunity to use placebos are better used on Europe’s less-treated population.
In the two clinical trials, the patients given Novantrone had fewer and less frequent flare-ups and slower disease progression, resulting in prolonged mobility.
“The MRIs show a dramatic decline of new lesions,” Gilbert said.
Officials at Immunex cite common side effects of the drug as nausea, hair loss, bladder and other infections, mouth sores, and changes in menstrual cycle and cardiac rhythm.”
Serious heart problems may develop in patients undergoing treatment because Novantrone accumulates within the patients’ systems.
The medication can only be used for two years or it becomes toxic. Once patients discontinue using the drug, their former stage of MS returns, Birnbaum said.

Mickie Barg covers the Medical School and welcomes comments at (612) 627-4070 x3223. He can also be reached at [email protected]