Fingolimod (Gilenya): An oral sphingosine 1-phosphate receptor modulator

December 1, 2010

New molecular entity: Fingolimod (Gilenya) has recently been approved by FDA to treat patients with relapsing forms of MS to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.

Fingolimod 0.5-mg capsules were approved to treat patients with relapsing forms of MS to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. Fingolimod is a sphingosine 1-phosphate receptor modulator and blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood and thus the number that can migrate into the central nervous system.

Efficacy. Fingolimod's efficacy has been assessed in 2 randomized, double-blind trials that evaluated once-daily doses of fingolimod 0.5 mg and 1.25 mg in patients with relapsing remitting MS (RRMS). Both studies included patients who had experienced at least 2 clinical relapses during the 2 years prior to randomization or at least 1 clinical relapse during the 1 year prior to randomization, and had an Expanded Disability Status Scale (EDSS) score from 0 to 5.5. The first trial was a 2-year, placebo-controlled trial in patients not receiving interferon-beta, glatiramer acetate, or natalizumab and found the annualized relapse rate to be significantly lower in patients treated with fingolimod than in patients who received placebo (0.18 vs 0.40; P<.001). In addition, disability progression was significantly delayed with fingolimod. The second trial was a 1-year, active-controlled trial in patients with RRMS. The annualized relapse rate was significantly lower in patients treated with fingolimod 0.5 mg than in patients who received interferon beta-1a intramuscularly (0.16 vs 0.33; P<.001).

Safety. The most common adverse reactions associated with fingolimod (occurring in ≥10% of patients and more often than placebo) include headache, liver transaminase elevations, influenza, diarrhea, back pain, and cough. Initiation of fingolimod was commonly associated with bradycardia and heart block. Patients receiving Class Ia or Class III antiarrhythmic drugs, beta blockers, calcium channel blockers, those with a low heart rate, history of syncope, sick sinus syndrome, second degree or higher conduction block, ischemic heart disease, or congestive heart failure are at increased risk of developing bradycardia or heart block. Fingolimod may increase the risk of infections and should not be started in patients with active acute or chronic infections. Other significant safety concerns with fingolimod requiring diligent monitoring include macular edema (0.4%) and decreases in pulmonary function tests.