Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
Gilenya (fingolimod) is a disease-modifying treatment for multiple sclerosis (MS) by Novartis.
It is approved by the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) for patients aged 10 and older with relapsing forms of MS. Its safety in children aged 10 years and older was similar to that seen in adults in a pediatric study.1,2 Gilenya was the first oral treatment available for the long-term treatment of relapsing-remitting multiple sclerosis (RRMS).3
In December 2019, the FDA approved the applications from HEC Pharm, Biocon, and Sun Pharmaceutical for generic versions of Gilenya for the treatment of adults with relapsing forms of the disease.4 Novartis holds the patent over Gilenya until 2027, and under a 2020 court decision, the company will decide which drug company will manufacture its generic version.
The recommended dosage of the treatment is 0.5 mg taken orally once a day for adults and children aged 10 years and older and weighing more than 40 kg, and 0.25 mg for those weighing less than 40 kg.1
Mechanism of Action
Gilenya blocks the action of the sphingosine-1-phosphate (S1P) receptor on T lymphocytes, thereby limiting their exit from the lymph nodes and their entry to the central nervous system (CNS). This minimizes the damage they cause to the myelin sheath.2
Warnings, Precautions, and Adverse Reactions
Gilenya treatment can cause serious side effects, including bradycardia, increased risk of opportunistic infections, including progressive multifocal leukoencephalopathy (PML) caused by the JC virus, vision impairment, CNS vasculitis, hepatic damage, respiratory issues, hypertension, and certain types of cancer.5
The most common side effects associated with Gilenya are headaches, abnormal liver test results, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, and pain in the arms or legs.
Get detailed prescribing information on the Gilenya monograph page on Rare Disease Advisor.
Based on findings from animal studies, Gilenya can cause harm to the fetus and should not be used by pregnant women due to increased toxicity. Women of reproductive age should use effective birth control while on Gilenya treatment and for at least 2 months following discontinuation, as this is how long it takes for the treatment to be eliminated from the body.
Efficacy in Clinical Trials
The approval of Gilenya was based on the results of double-blind, randomized phase 3 clinical trials performed to assess its safety and efficacy.
The first trial, called FREEDOMS, was a 24-month, double-blind, randomized, multicenter, placebo-controlled, parallel-group study that compared the safety and efficacy of 2 doses of once-daily Gilenya (1.25 mg and 0.5 mg) to a placebo in patients with RRMS.6 The primary objective of the study was the estimated annualized aggregate relapse rate from baseline to the end of the study.
The trial enrolled 1272 patients with RRMS, aged 18 to 55 years, of whom 1033 completed the study. All participants had a score of 0 to 5.5 on the Expanded Disability Status Scale (EDSS) and had had 1 or more relapses in the previous year or 2 or more relapses in the previous 2 years. Patients with chronic diseases, acute pulmonary disease, or cardiac failure as well as female patients who were pregnant or nursing were excluded from the trial.
The results showed that both doses of Gilenya improved the relapse rate, the risk of disability progression, and endpoints on MRI compared to placebo.7
The second trial, FREEDOMS II, was a study consisting of 2 phases.8 The first phase was a 24-month double-blind, randomized, multicenter, placebo-controlled, parallel-group study, while the second was an extension phase consisting of a dose-blinded period and an open-label period. The primary outcome measure of the trial was the aggregate annualized relapse rate.
The study enrolled 1083 participants with RRMS, aged 18 to 55 years, to receive either 0.5 mg of Gilenya, 1.25 mg of Gilenya, or placebo once a day.
The results showed significant reduction in the annualized relapse rate in patients receiving 0.5 mg of Gilenya compared to those receiving placebo.9 The percentage of brain volume change was lower in patients given 0.5 mg of Gilenya compared to patients given placebo. There were no statistically significant differences between groups in confirmed disability progression.
The third trial, TRANSFORMS, was a 12-month double-blind, randomized, multicenter, active-controlled, parallel-group study comparing the safety and efficacy of 0.5 mg and 1.25 mg of once-daily Gilenya to that of Avonex® in patients with RRMS.10 The primary outcome of the study was the estimated annualized aggregate relapse rate.
The study enrolled 1292 patients with RRMS who had a recent history of at least 1 relapse. Patients were given either 1.25 mg of Gilenya, 0.5 mg of Gilenya, or Avonex. A total of 1153 patients completed the study.
Results showed that the annualized relapse rate was significantly lower in both groups receiving Gilenya compared to Avonex.11 There were no significant differences between groups in terms of disability progression.
Another Phase 3 clinical trial called LONGTERMS assessed the long-term efficacy of Gilenya treatment in 3480 patients, aged 17 to 65 years.12
Results showed that patients receiving Gilenya had sustained low levels of disease activity and progression confirming the treatment’s established safety profile.13
Gilenya’s safety and efficacy in pediatric patients were tested in a double-blind, randomized, multicenter trial called PARADIGMS in 215 patients aged 10 to 17 years with MS.14 The trial compared Gilenya with interferon beta-1a.
The results showed that Gilenya treatment was linked with a lower relapse rate and less accumulation of lesions shown on MRI over 2 years compared to interferon beta-1a.15 However, it was also associated with a higher rate of serious adverse events.
1. Gilenya. Package insert. Novartis; 2010. Updated May 2018. Accessed June 14, 2021.
2. Gilenya. European Medicines Agency. Accessed June 14, 2021.
3. FDA approves first oral treatment for relapsing forms of MS. Multiple Sclerosis Association of America. September 23, 2010. Accessed June 17, 2021.
4. FDA approves generic versions of Gilenya®. News release. Multiple Sclerosis Association of America; December 6, 2019.
5. What to know about the safety of Gilenya® (fingolimod). Novartis. Accessed June 14, 2021.
6. Efficacy and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS). ClinicalTrials.gov. Updated April 11, 2012. Accessed June 14, 2021.
7. Kappos L, Radue E, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;4;362(5):387-401. doi:10.1056/NEJMoa0909494
8. Efficacy and safety of fingolimod (FTY720) in patients with relapsing-remitting multiple sclerosis (FREEDOMS II). ClinicalTrials.gov. Updated August 7, 2012. Accessed June 14, 2021.
9. Calabresi P, Radue E, Goodin D, et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(6):545-556. doi:10.1016/S1474-4422(14)70049-3
10. Efficacy and safety of fingolimod in patients with relapsing-remitting multiple sclerosis with optional extension phase (TRANSFORMS). ClinicalTrials.gov. Updated September 21, 2017. Accessed June 14, 2021.
11. Cohen J, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;4;362(5):402-415. doi:10.1056/NEJMoa0907839
12. Long-term safety and tolerability of 0.5 mg fingolimod in patients with relapsing forms of multiple sclerosis. ClinicalTrials.gov. Updated April 21, 2021. Accessed June 14, 2021.
13. Cohen J, Tenenbaum N, Bhatt A, Zhang Y, Kappos L. Extended treatment with fingolimod for relapsing multiple sclerosis: the 14-year LONGTERMS study results. Ther Adv Neurol Disord. 2019;12:1756286419878324. doi:10.1177/1756286419878324
14. Safety and efficacy of fingolimod in pediatric patients with multiple sclerosis. ClinicalTrials.gov. Updated May 12, 2021. Accessed June 14, 2021.15. Chitnis T, Arnold D, Banwell B, et al. Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med. 2018;13;379(11):1017-1027. doi:10.1056/NEJMoa1800149
Reviewed by Debjyoti Talukdar, MD, on 7/1/2021.