General Information

Gilenya is a sphingosine 1-phosphate receptor modulator. The exact mechanism is unknown, but Gilenya is thought to work by reducing the immune system's attack on the central nervous system by retaining certain white blood cells (lymphocytes) in the lymph nodes.

Gilenya is specifically indicated for the treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.

Gilenya is supplied as a capsule designed for oral administration. The recommended initial dose is 0.5 mg orally once daily, with or without food.

Clinical Results

FDA Approval
The FDA approval of Gilenya was based on two clinical studies.
Study One
This 2-year randomized, double-blind, placebo-controlled study in 1,272 patients with RRMS who had not received any interferon-beta or glatiramer acetate for at least the previous 3 months and had not received any natalizumab for at least the previous 6 months. The subjects received Gilenya 0.25mg, 1.25mg or placebo for up to 24 months. The primary endpoint was the annual relapse rate. The 1.25 mg dose resulted in no additional benefit over the 0.5 mg dose. Results are as follows: Annualized relapse rate 0.18 for Gilenya 0.5mg vs. 0.40 for placebo (p<0.001). Percentage of patients without relapse: 70% for Gilenya 0.5mg vs. 46% for placebo (p<0.001). The mean (median) number of new or newly enlarging T2 lesions over 24 months was 2.5 for Gilenya 0.5mg vs. 9.8 for placebo (p<0.001).
Study Two
This 1-year randomized, double-blind, double-dummy, active-controlled study enrolled 1,292 subjects with RRMS who had not received any natalizumab in the previous 6 months. The subjects were randomized to receive Gilenya 0.5 mg, 1.25 mg or interferon beta-1a, 30 micrograms via the intramuscular route (IM) once weekly for up to 12 months. The annualized relapse rate was significantly lower in patients treated with Gilenya 0.5 mg than in patients who received interferon beta-1a IM. The 1.25 mg dose resulted in no additional benefit over the Gilenya 0.5 mg dose. The results are as follows: Annualized relapse rate 0.16 for Gilenya 0.5mg vs. 0.33 for Interferon beta-1a (p<0.001). Percentage of patients without relapse: 83% for Gilenya 0.5mg vs. 70% for Interferon beta-1a (p<0.001). The mean (median) number of new or newly enlarging T2 lesions over 24 months was 1.6 for Gilenya 0.5mg vs. 2.6 for IFN beta (p=0.002).

Mechanism of Action

Gilenya is a sphingosine 1-phosphate receptor modulator and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.

Literature References

Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L, Burtin P; FREEDOMS Study Group A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. The New England Journal of Medicine 2010 Feb 4;362(5):387-401

Comi G, O'Connor P, Montalban X, Antel J, Radue EW, Karlsson G, Pohlmann H, Aradhye S, Kappos L; FTY720D2201 Study Group Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results. Multiple Sclerosis 2010 Feb;16(2):197-207

Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, Haas T, Korn AA, Karlsson G, Radue EW; FTY720 D2201 Study Group Oral fingolimod (FTY720) for relapsing multiple sclerosis. The New England Journal of Medicine 2006 Sep 14;355(11):1124-40.