January 30, 2012

Investigating Fingolimod for Multiple Sclerosis

(Ivanhoe Newswire)-- Many of us have heard of or know someone with the dreadful disease known as multiple sclerosis. Affecting approximately 400,000 people in the United States and 2.5 million people worldwide, multiple sclerosis is still incurable and has few effective treatments available.

Patients affected by multiple sclerosis are hindered on a daily basis by physical ailments, including fatigue, pain, and difficulty with mobility, as well as problems with social functioning and impaired mood.

The Food and Drug Administration (FDA) approved fingolimod in September 2010, as a treatment targeted at reducing the frequency of clinical exacerbations and postponing the progression of physical disability in patients with relapsing forms of multiple sclerosis. Fingolimod was the first oral therapy approved by the FDA for the treatment of multiple sclerosis.

Multiple sclerosis is an autoimmune disease in which lymphocytes move out of lymph nodes into the circulation, cross the blood—brain barrier, and aggressively target putative myelin antigens in the central nervous system, causing inflammation, demyelination, neuroaxonal injury, astrogliosis, and eventually neurodegeneration.

Although patients with multiple sclerosis that are treated with fingolimod have a reduction in the overall mean lymphocyte count, the effects on lymphocyte subsets are rather specific: the drug blocks the exit of naive and central memory lymphocytes, but not effector memory T cells, from the lymph node.

The effectiveness of oral fingolimod for the treatment of multiple sclerosis was investigated in a study consisting of two large, phase 3, double-blind, randomized trials involving patients with relapsing—remitting disease. Patients with progressive forms of multiple sclerosis were not included in the study.

The study consisted of 1272 patients who were randomly assigned to receive oral fingolimod at a dose of 0.5 mg daily or 1.25 mg daily or placebo tablets for 2 years. 22 Neurologic evaluations included measures of acute relapses and disability.

Fingolimod was shown to reduce the frequency of clinical exacerbations and delay the progression of physical disability in patients with reoccurring forms of multiple sclerosis. Fingolimod was also associated with a reduced amount of new or enlarging lesions on T2-weighted images and of gadolinium-enhancing lesions on MRI at year 2. Reductions in whole-brain volume were smaller with fingolimod than with placebo at both 12 and 24 months.

Despite the positive results in the trials, researchers believe that until additional long-term safety information is available, fingolimod therapy should be considered only for patients who have had recent inflammatory disease activity and those who do not benefit from or cannot tolerate alternative disease-modifying therapies.

SOURCE: New England Journal of Medicine, January 2012