Gilenya (fingolimod), manufactured by Novartis, is an oral treatment approved by the U.S. Food and Drug Administration (FDA) for patients with relapsing forms of multiple sclerosis (MS) ages 10 and older. Relapsing MS includes people with clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (active SPMS).
In the European Union, Gilenya is approved to treat adults with relapsing forms of MS, and children, ages 10 and older, with RRMS.
This disease-modifying therapy modulates the immune response and works to reduce disease exacerbations, to delay the progression and accumulation of disability.
How Gilenya works
In multiple sclerosis (MS), the immune system mistakenly targets healthy myelin, the main component of the insulating and protective sheath that surrounds nerve fibers. Immune cells, or lymphocytes, can freely cross the blood-brain barrier and cause inflammation and damage to the brain and spinal cord, resulting in progressive nerve cell death (neurodegeneration).
Gilenya is a type of sphingosine 1-phosphate (S1P) receptor modulator. S1P receptors are present on the outside of the lymphocytes and have various roles, including regulating the lymphocytes leaving the lymph nodes, where they are made and stored.
By binding to the S1P receptor, Gilenya acts to retain lymphocytes in the lymph nodes and prevent them from reaching the brain and spinal cord. This should lower the number of lymphocytes in the brain, reducing inflammation and damage.
S1P receptors are also found on some cells of the brain and spinal cord. By binding to these cells, Gilenya may promote their survival and growth, potentially stimulating re-myelination.
Gilenya in clinical trials
Gilenya was approved by the FDA in September 2010 to treat RRMS in patients age 18 and older, based on the results of three key Phase 3 clinical trials: FREEDOMS (NCT00289978), FREEDOMS II (NCT00355134), and TRANSFORMS (NCT00340834).
FREEDOMS enrolled 1,272 RRMS patients, ages 18-55, at trial sites worldwide. Over a two-year period, patients were given Gilenya at a low or high dose, or a placebo, daily. Results, published in the New England Journal of Medicine, demonstrated that Gilenya significantly reduced the number of relapses and slowed disability progression.
The TRANSFORMS study compared Gilenya to another established MS therapy, Avonex (interferon beta-1a), over the course of one year. A total of 1,153 RRMS patients who had recently relapsed were enrolled at trial sites worldwide. The results, published in the New England Journal of Medicine, suggested that Gilenya was more effective than Avonex in reducing the number of relapses, supported by brain imaging scans showing fewer lesions. No significant difference in the progression of disability was seen between the two treatments.
On May 11, 2018, the FDA extended Gilenya’s approval to include pediatric relapsing MS patients, age 10 or older, based on the results of a Phase 3 clinical trial (NCT01892722) called PARADIGMS. The trial enrolled 215 children with relapsing MS, ages 10-18, and randomized them to receive either Gilenya or Avonex for up to two years. Results, published in The New England Journal of Medicine, demonstrated that treatment with Gilenya was associated with a lower relapse rate and fewer additional brain lesions as detected by magnetic resonance imaging (MRI). However, a high rate of serious adverse events was reported, including infection in four patients and leukopenia, or a low white blood cell count, in two patients.
The Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency, also supported Gilenya as a treatment for RRMS in children in a favorable opinion to the EMA in September 2018. A label extension was approved by the European Commission in November 2018.
A long-term Phase 3, open-label extension protocol (NCT01201356) investigated the safety and efficacy of Gilenya in 4086 patients. The trial was nicknamed LONGTERMS and included patients from all previous studies. Participants were given 0.5 mg doses of Gilenya once daily. The results of the study were published in Therapeutic Advances in Neurological Disorders and showed that 45.5% of patients remained free of relapses after a decade of treatment and 63.2% showed no signs of worsening disability.
Common side effects associated with Gilenya include dizziness, headaches, nausea, and fatigue. Because the treatment modulates the immune system, patients with infectious diseases should avoid using it, as these infections may worsen as the result of a temporarily less active immune system.
The FDA announced in May 2012 that Gilenya is contraindicated in patients with certain pre-existing or recent heart conditions or stroke, or who are taking certain anti-arrhythmic medications. Pregnant women are also advised not to take Gilenya.
The FDA also issued a safety alert in November 2018, warning of a risk of worsening disability within weeks or months of stopping Gilenya’s use. While this risk is rare, the agency noted that it can be severe and result in permanent disability.
Last updated: Dec. 10, 2019
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