For US Health Care Professionals Only

MOA

Targeted MOA redistributes lymphocytes without destroying them1,14,15*

The mechanism by which GILENYA exerts therapeutic effects in MS is unknown but may involve reduction of lymphocyte migration into the CNS. The mechanism of action (MOA) for GILENYA was observed in animal models.
Targeted mechanism of action (MOA) redistributes lymphocytes without destroying them

Watch how GILENYA is thought to sequester certain inflammatory T cells

  • GILENYA binds to sphingosine-1 phosphate receptors 1,4 on certain lymphocytes (T cells)14
  • This keeps these lymphocytes in the lymph nodes, where they are stored, not destroyed.14 They remain functional within the lymph nodes
  • Blood lymphocyte counts are expected to decrease by 70% to 80% of baseline1
The CBC does not measure a total body lymphocyte count. Only those circulating in the blood are measured, not those in the tissues-which is where ~98% of lymphocytes reside. Just ~2% of the total lymphocyte count is circulating in the bloodstream at any given time. This is why patients taking GILENYA may have low CBCs. Blood lymphocyte counts are decreased, but not total body count.14,20-22
  • * Monitor for signs and symptoms of infection during treatment and for 2 months after discontinuation. Do not start GILENYA treatment in patients with active acute or chronic infections.
    • The immune system can still mount a response14
    • In clinical trials, the overall rate of infection with GILENYA was similar to placebo
      • Although bronchitis, herpes zoster, influenza, sinusitis, and pneumonia were more common with GILENYA
    • GILENYA may increase the risk of infections, some serious in nature1
    • Life threatening and fatal infections have occurred in association with GILENYA
    Incidence of infections in adult patients from pooled results of FREEDOMS and FREEDOMS II 1,7,13
    Incidence of infections and serious infections in FREEDOMS
    • After discontinuation, lymphocytes typically returned to pretreatment values within 1 to 2 months1
  • * Monitor for signs and symptoms of infection during treatment and for 2 months after discontinuation. Do not start GILENYA treatment in patients with active acute or chronic infections.
  •  
    References: 1. Gilenya [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; May 2018. 2. Kappos L, Radue E-W, O’Connor P, et al; for FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387-401. 3. Cohen JA, Barkhof F, Comi G, et al; for TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402-415. 4. Data on file. Summary of Clinical Efficacy in Multiple Sclerosis. Novartis Pharmaceuticals Corp; East Hanover, NJ. November 2009. 5. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability scale (EDSS). Neurology. 1983;33(11):1444-1452. 6. Data on file. CSR 2302. Novartis Pharmaceuticals Corp; East Hanover, NJ. July 2009. 7. Data on file. CSR 2301. Novartis Pharmaceuticals Corp; East Hanover, NJ. July 2009. 8. Ge Y. Multiple sclerosis: the role of MR imaging. AJNR Am J Neuroradiol. 2006;27(6):1165-1176. 9. Hauser SL, Goodin DS. Multiple sclerosis and other demyelinating diseases. In: Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: The McGraw-Hill Companies, Inc; 2008:2611-2621. 10. Data on file. Briefing document. Novartis Pharmaceuticals Corp; East Hanover, NJ. May 2010. 11. Data on file. GILENYA exposure: May 2018 cutoff. Novartis Pharmaceuticals Corp; July 2018. 12. Data on file. Hub SRF and Sales Table. Novartis Pharmaceuticals Corp. Q4 2017. 13. Data on file. CSR 2309. Novartis Pharmaceuticals Corp; East Hanover, NJ. July 2009. 14. Chun J, Hartung H-P. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol. 2010;33(2):91-101. 15. Takabe K, Paugh SW, Milstien S, Spiegel S. “Inside out” signaling of sphingosine-1-phosphate: therapeutic targets. Pharmacol Rev. 2008;60(2):181-195. 16. Data on file. GILENYA exposure: February 2018 cutoff. Novartis Pharmaceuticals Corp; May 2018. 17. DiMarco JP, O’Connor P, Cohen JA, et al. First-dose effects of fingolimod: pooled safety data from three phase 3 studies. Mult Relat Disord. 2014;3(5):629-638. 18. Degaute JP, van de Borne P, Linkowski P, et al. Quantitative analysis of the 24-hour blood pressure and heart rate patterns in young men. Hypertension. 1991;18(2):199-210. 19. Zdanowicz MM, Lynch LM. Teaching the pharmacology of antiarrhythmic drugs. Am J Pharm Educ. 2011;75(7):139. 20. Ganusov VV, De Boer RJ. Do most lymphocytes in humans reside in the gut? Trends Immunol. 2007;28(12):514-518. 21. Zhang ZQ, Notemans DQ, Sedgewick G, et al. Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection. Proc Natl Acad Sci U S A. 1998;95(3):1154-1159. 22. Haynes BF, Soderberg KA, Fauci AS. Introduction to the immune system. In: Fauci AS, ed. Harrison’s Rheumatology. 2nd ed. New York, NY: The McGraw-Hill Companies; 2010:2-43. 23. Aubagio [prescribing information]. Cambridge, MA: Genzyme Corp; October 2014a.