Gilenya (fingolimod) is an oral treatment for multiple sclerosis (MS) that works to reduce disease exacerbations, delay the progression of disability, and prevent the development of new brain lesions. It is manufactured by Novartis, which was granted a U.S. patent covering a dosing regimen for the therapy.
Several generic forms of Gilenya have been approved in the U.S. since 2019 — but a court ruling blocked these medications from being marketed in the country. Under a new appeals court ruling issued in early 2022, generic forms of Gilenya in the U.S. are not expected to be commercially available until at least 2024, according to Novartis. The company also issued a press release in February announcing a decision by the European Patent Office on generics.
To date, Gilenya has been approved in more than 50 countries, as well as in the EU. Other countries include Australia, Brazil, Canada, China, and Japan.
In MS, the immune system mistakenly attacks and damages myelin, the fatty substance that covers nerve fibers and is essential for rapid and effective nerve communication.
Gilenya is a type of sphingosine 1-phosphate (S1P) receptor modulator. S1P receptors are expressed on the surface of certain immune cells, and are important for regulating the movement of these cells from lymph nodes — where they are matured and stored — to the blood.
By modulating these receptors, Gilenya “traps” immune cells inside lymph nodes. This prevents these inflammatory cells from getting into the nervous system and causing damage.
S1P receptors also are found on some cells in the brain and spinal cord, such as nerve cells and oligodendrocytes, the cells chiefly responsible for making myelin. By binding to these cells, Gilenya may promote their survival and growth, potentially supporting nervous system health.
The U.S. Food and Drug Administration first approved Gilenya in 2010 to treat adults with relapsing forms of MS, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
That approval was later expanded in 2018 to include children and adolescents ages 10 and older, making Gilenya the first disease-modifying therapy available for pediatric MS patients.
In the European Union, Gilenya is only indicated for people with RRMS who have highly active disease. It was approved for adults in 2011 and expanded to children and adolescents ages 10 and older in 2018.
Gilenya is not recommended for anyone who:
Gilenya is available in hard gelatin capsules, taken orally, that come in two strengths:
The recommended dose of Gilenya for adults and children who weigh at least 40 kg (about 88 pounds) is 0.5 mg, taken orally once daily. For children weighing less than 40 kg, the dose is 0.25 mg per day.
Gilenya may be taken with or without food and should be stored at room temperature.
The first dose of Gilenya can cause a decrease in heart rate. Thus, patients starting on the medication for the first time, or restarting it after not using the therapy for at least two weeks, should have their pulse and blood pressure monitored regularly for six hours after the first dose. An electrocardiogram (ECG) — a test of the heart’s rhythm and electrical activity — also should be performed before dosing and again after six hours. Patients who show signs of heart problems may require additional monitoring.
Possible sites where these first-dose observation steps may be completed include:
Gilenya’s approval for adults was based on data from three key Phase 3 clinical trials: FREEDOMS (NCT00289978), FREEDOMS II (NCT00355134), and TRANSFORMS (NCT00340834). Its use in children is supported by data from the PARADIGMS Phase 3 trial (NCT01892722), which is ongoing.
The Novartis-sponsored FREEDOMS trial enrolled 1,272 adults with RRMS, ages 18-55, at trial sites worldwide. Over a two-year period, patients were given Gilenya (0.5 mg or 1.25 mg), or a placebo, daily. Results demonstrated that the 0.5 mg dose of Gilenya significantly reduced relapse rates by 54% and slowed disability worsening lasting at least three months by 30%. Patients on this dose also had significantly fewer new or enlarging brain lesions, and reduced brain volume loss.
A similarly designed trial called FREEDOMS II, also sponsored by Novartis, enrolled 1,083 people with RRMS. Participants were given Gilenya or a placebo for two years. The results were generally consistent with data from the FREEDOMS trial. However, no differences in confirmed disability progression between patients given a placebo and on the 0.5 mg dose were observed in this trial.
The TRANSFORMS study compared Gilenya with an approved MS therapy, Avonex (interferon beta-1a), over the course of one year. A total of 1,153 RRMS patients, ages 18-55, were enrolled at trial sites worldwide.
This study found that treatment with Gilenya, at a daily dose of 0.5 mg, resulted in a significantly lower relapse rate compared with Avonex (0.16 vs. 0.33 relapses per year). Gilenya-treated participants also had significantly fewer additional brain lesions on MRI scans and smaller changes in brain volume. However, rates of disability progression were not significantly different between the two medications.
An open-label study called LONGTERMS (NCT01201356) enrolled 4,086 adults with RRMS who had participated in the FREEDOMS or TRANSFORMS trials or in other clinical studies of Gilenya. All received the therapy at a daily dose of 0.5 mg. After a decade of treatment, 45.5% of patients remained free of relapses, and 63.2% had not experienced confirmed worsening disability lasting at least six months.
The PARADIGMS trial (NCT01892722), which formed the basis for extending Gilenya to children ages 10 and older, enrolled 215 children with relapsing MS, ages 10-17. Participants were randomly assigned to receive either Gilenya — at a dose of 0.5 mg, or 0.25 mg for those weighing 40 kg or less — or Avonex for up to two years.
Findings from this trial showed that Gilenya significantly reduced the annualized relapse rate by 82% compared with Avonex. Treatment with Gilenya also resulted in 53% fewer new or enlarging brain lesions on MRI scans and smaller changes in brain volume. Additional analyses also demonstrated that significantly fewer patients on Gilenya experienced three-month confirmed disability progression. The study is still underway and is expected to conclude by 2028.
In China, Novartis is conducting an open-label Phase 4 clinical trial (NCT04667949). That trial is evaluating Gilenya for up to one year in about 100 Chinese patients with relapsing MS. A similar open-label Phase 4 trial called SPRING (NCT04480853) is testing the medication in an estimated 30 Taiwanese adults with RRMS.
Novartis also is running a trial called NEOS (NCT04926818), which is seeking to recruit 180 children and adolescents with MS, ages 10 to 17. The study will compare the safety and effectiveness of Gilenya against two other approved treatments for relapsing MS. Specifically, it is testing the therapy against Mayzent (siponimod) and Kesimpta (ofatumumab).
The most common side effects associated with Gilenya include:
Gilenya may increase the risk of infections. Blood cell counts should be checked prior to starting on the medication, and patients should be monitored for signs of infection while on Gilenya and for two months after stopping the therapy. Gilenya should not be given to people with an active infection. Vaccines that contain a live virus should not be administered to patients during treatment.
Cases of progressive multifocal leukoencephalopathy (PML), a rare and potentially deadly brain infection, have been reported in patients on Gilenya. The therapy should be stopped at the first sign of this infection.
In rare cases, adults treated with Gilenya can experience posterior reversible encephalopathy syndrome (PRES), a neurological disorder characterized by symptoms like a sudden, severe headache, changes in mental status, impaired vision, and seizures. Gilenya should be discontinued if patients show signs of PRES.
Gilenya can cause liver injury. Markers of liver health should be assessed prior to starting the treatment and also if patients show any signs of liver damage. If significant liver injury is confirmed, treatment with Gilenya should be ceased.
Treatment with Gilenya increases the risk of macular edema, a form of swelling in the eye, particularly in people with diabetes or a type of eye inflammation called uveitis. Retinal health should be checked before starting on Gilenya, after three to four months on the therapy, and at any time patients report unexpected vision problems. Those who develop macular edema are advised to talk to their healthcare providers about the potential benefits and risks of continuing on Gilenya.
Starting on Gilenya typically causes a decrease in heart rate, and the medication may cause abnormal heart rhythms or interfere with the heart’s electrical activity. Heart health should be monitored when starting on Gilenya, and the medication is not recommended for individuals with certain heart conditions. High blood pressure also can occur as a side effect of Gilenya, and blood pressure should be monitored during treatment.
Some people treated with Gilenya experience a decline in lung function, which can cause symptoms such as shortness of breath. If patients show signs of lung problems, a full workup of lung health should be performed.
Allergic reactions including rash, hives, and swelling have been reported in patients treated with Gilenya. The therapy should not be given to anyone with a known allergy, and should be stopped if patients develop an allergic response.
Gilenya increases the risk of certain skin cancers, particularly basal cell carcinoma and melanoma. Skin examinations should be regularly performed, and any suspicious lesions should be promptly evaluated. Gilenya-treated patients are advised to follow usual guidelines for people at high risk of skin cancer. In particular, patients taking the medication are recommended to use sunscreen or protective coverings to limit sunlight exposure.
Lymphomas, or cancers that start in the immune system, also have been reported in Gilenya-treated patients.
Some people with MS have experienced a severe worsening in disability and multiple new lesions on MRI scans upon stopping Gilenya treatment. This worsening typically occurs within three months of stopping therapy, but can happen later. Patients who stop Gilenya treatment should be monitored for disability worsening, and given appropriate treatments as needed.
Gilenya remains in the body and continues to exert biological effects, including reducing immune cell counts, for up to two months after the treatment is stopped.
Gilenya has not been well studied during pregnancy or breastfeeding in MS patients. Animal studies suggest that the medication can cause harm to a developing fetus and that it is excreted in breast milk.
It is recommended that patients with the potential to become pregnant use effective contraception while taking Gilenya and for at least two months after discontinuing treatment. The potential benefits and risks of using Gilenya while breastfeeding should be discussed between patients and their healthcare team.
Those who become pregnant while on Gilenya may enroll in a Novartis-sponsored registry (NCT01285479) that is monitoring pregnancy outcomes with Gilenya exposure.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
The U.S. Food and Drug Administration (FDA) first approved Gilenya in 2010 to treat adults with relapsing forms of MS. These include clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. The FDA then expanded the approval in 2018 to cover children as young as age 10.
Gilenya has not been well-studied in humans during pregnancy, but animal data suggest that it can harm a developing fetus. Patients who have the potential to become pregnant are recommended to use effective contraception while on Gilenya, and for at least two months after stopping treatment.
There is no known interaction between alcohol and Gilenya. However, since alcohol can interfere with some medications and disease symptoms, it is recommended that patients talk about this issue with their healthcare providers.
Some patients may see results as early as six months after starting treatment. In the FREEDOMS trials, which collectively compared Gilenya against a placebo in more than 2,000 patients with relapsing-remitting MS, a significantly smaller brain volume loss was evident with Gilenya as soon as six months after treatment start. However, each multiple sclerosis patient is unique and may have different manifestations of the disease; individuals also may respond differently to the medication. A discussion with their healthcare team can help patients understand how the medication may help in their specific case.
Changes in body weight were not reported in clinical trials as side effects of Gilenya, but some people who received the medication in the FREEDOMS trials experienced hair loss. Patients who experience unanticipated effects of treatment should discuss these with their care team.
Get regular updates to your inbox.