Experimental Drug Fights Multiple Sclerosis Activity
It led to a reduction of lesions seen on MRIs with limited side effects, study found
FRIDAY, June 20, 2008 (HealthDay News) -- One of the first pills to treat the "relapse-remitting" form of multiple sclerosis has been shown to help fight the disease with few side effects.
Although the drug, laquinimod, is still experimental, having a pill available would make therapy much more convenient for many patients.
"By and large, this doesn't look as strong as the strongest injectable drugs like Tysabri... but, in general, I believe that patients and companies feel that the advantage of having an oral drug makes these attractive additions to our therapeutic armamentarium," said Dr. John Richert, executive vice president for research and clinical programs at the National Multiple Sclerosis Society.
"Patients are more likely to stay on an oral drug. We'll need to see what comes out of Phase 3 trials [the current trial was a Phase 2 study]. At this point, it's encouraging, and certainly patients are thirsting for oral options," Richert added.
The study, funded by Teva Pharmaceutical Industries, is published in the June 21 issue of The Lancet. Earlier results from the same trial were presented this spring at the annual meeting of the American Academy of Neurology.
Multiple sclerosis affects the central nervous system and is thought to be an autoimmune disease. It primarily strikes "white matter" -- the tissues in the brain and the other parts of the nervous system that transmit messages between "gray matter," where nerve bodies are found. Symptoms range from the mild (numbness in the limb) to severe, including paralysis and loss of vision. There are four different "courses" of the disease, the most common being relapse-remitting MS, in which flare-ups alternate with partial or complete remissions.
Several treatments are available for MS; all are injectable.
Testing of an earlier, related oral drug called Linomide (roquinimex) was stopped during Phase 3 trials when the compound was linked to a high incidence of heart problems, including heart attacks. The trial lasted long enough, however, to show that the drug had benefit, Richert said.
"That information served as impetus for researchers to go back to the laboratory and try to engineer out the cardiac toxic part of the molecule but maintain the immunomodulatory effects that were beneficial for an autoimmune disease like multiple sclerosis," Richert explained. "That is how laquinimod was born."
Laquinimod works by binding to receptors on immune cells, isolating them in the lymph nodes, thereby reducing their ability to cause the damage associated with MS symptoms.
The nine-country study involved 306 patients aged 18 to 50 who were randomly assigned to receive either a placebo, 0.3 milligrams of laquinimod or 0.6 milligrams of laquinimod daily.
People with the higher dose of laquinimod had a 40.4 percent reduction in the number of lesions -- indicating disease activity -- seen on MRI scans. The lower dose had no significant benefit.
There were two side effects, both of them reversible. Two patients stopped taking the drug because they developed liver problems, the researchers said.
A Phase 3 trial is currently under way, said the study authors, from the Institute of Experimental Neurology at the University Vita-Salute in Milan, Italy.
"Certainly there have been Phase 2 drugs that have looked OK that have failed in Phase 3," Richert said. "There's always a significant amount of guesswork in trying to predict how things are going to end up."
Visit the National Multiple Sclerosis Society for more on this disease.