Gilenya® (fingolimod, FTY720)
Novartis Pharmaceuticals Corp.
- Oral medication; 0.5 mg capsule taken once daily.
- Approved for relapsing forms of multiple sclerosis (MS).
- Gilenya (pronounced as "Jil-EN-ee-ah") is the first in a new class of immunomodulatory drugs, called S1P-receptor modulators. Gilenya is similar in structure to a naturally occurring component of cell surface receptors on white blood cells. It blocks potentially damaging T cells from leaving lymph nodes, lowering their number in the blood and tissues. It may reduce damage to the CNS and enhance the repair of damaged neurons. Animal data suggest that Gilenya may have neuroprotective effects.
- In September 2010, the FDA approved this drug as a first-line treatment for relapsing forms of MS. Gilenya is the first oral disease-modifying therapy available for the long-term treatment of MS.
- The most commonly reported side effects with Gilenya include headache, flu, diarrhea, back pain, abnormal liver tests and cough. Women are strongly advised to use contraception to avoid pregnancy while taking Gilenya - and to continue contraception for two months following the discontinuation of the drug. The makers of Gilenya also strongly advise against breastfeeding.
- Adverse events with Gilenya include: a reduction in heart rate (dose-related and transient); infrequent transient AV conduction block of the heart; a mild increase in blood pressure; macular edema (a condition that can affect vision, caused by swelling behind the eye); reversible elevation of liver enzymes; and a slight increase in lung infections (primarily bronchitis). Other infections, including Herpes infection, are also of concern.
- A number of precautionary steps have been put in place to minimize risks and enable doctors to better evaluate and treat any possible adverse events. Within six months prior to starting Gilenya, patients should be given a baseline evaluation of any issues with the heart, lungs, liver, eyes and vision, as well as white blood cell count (which may indicate an existing infection). Present medications also need to be considered. Vitals (blood pressure, pulse, etc.) should be taken at baseline and periodically while on treatment.
- Since the drug causes a reduction in circulating white blood cells, individuals considering Gilenya also need to indicate if they have had chicken pox or a chicken pox vaccination recently; if so, they may need to wait before starting the medication. Individuals who test negative for the chicken pox virus may need to be vaccinated and delay starting Gilenya. Patients will also need to avoid vaccinations with live viruses.
- When beginning the drug, patients must be observed at a medical facility for the first six hours following the first dose. This is necessary as Gilenya may slow the heart rate, with the most significant drop usually occurring within the first six hours. While taking this drug, patients need to contact their doctor immediately if they experience any symptoms such as dizziness, tiredness, slow or irregular heartbeat, breathing difficulties, visual changes, or signs of an infection or liver problem.
- A Risk Evaluation and Mitigation Strategy (REMS) has been approved to provide information to patients as well as healthcare professionals on how to use the drug safely, along with possible risks that may occur. Novartis will conduct a five-year observational safety study to further evaluate any adverse events. They have also organized a voluntary registry for women who become pregnant while taking or within two months after discontinuing Gilenya to document possible effects.
- The FREEDOMS Phase III study of low-dose (0.5 mg) and high-dose (1.25 mg) Gilenya versus placebo is scheduled to end in March 2011. Outcome measures to date show the drug to be safe and well tolerated. Interim data show a 60-percent reduction in annualized relapse rate, a significant reduction in disability progression, a 74 to 82-percent reduction in the burden of disease as measured by MRI, and a reduction in whole-brain atrophy.
- An extension study, FREEDOMS II, evaluated long-term safety, tolerability and efficacy; all 1,080 participants received Gilenya. Two deaths resulted from Herpes virus infection in the FREEDOMS trials; both of these individuals had received a higher dose than that submitted to the FDA. No deaths were reported in the lower-dose group, which used the same dose as approved by the FDA.
- The TRANSFORMS Phase III trial was a 12-month study of the efficacy of two doses of Gilenya (0.5 mg and 1.25 mg) as compared to weekly intramuscular injections of Avonex in individuals with RRMS. Its primary outcome measure was a reduction of relapse rate. Secondary measures included frequency of relapses, inflammatory disease activity as measured on MRI, and time to progression of disability.
- In the TRANSFORMS trial, the annualized relapse rate was lower with Gilenya 0.5 mg (0.16) versus Avonex (0.33) at 12 months. The proportion of relapse-free patients was also higher with Gilenya. In summary, Gilenya was more effective in reducing relapse rate and relapse frequency, resulted in less deterioration in the ability to independently perform daily activities, was associated with a lower rate of brain atrophy, and showed a greater effect on reducing MRI measures of lesion activity.
- Another new clinical trial began in April 2010. It has 1,850 participants, all of whom are receiving Gilenya. This trial is scheduled for completion in April 2011. The primary outcome measure is the safety and tolerability profile in patients with relapsing forms of MS. Secondary measures include the incidence of macular edema (swelling behind the eye) and any changes in heart rate or function as seen on an electrocardiogram. Secondary measures also include patient-reported outcomes based on surveys of health status and treatment satisfaction.
- The 36-month INFORMS study in 940 individuals is the only trial now ongoing for primary-progressive MS (PPMS). It will evaluate the effect of Gilenya relative to placebo on delaying the time to sustained disability progression, as well as safety, tolerability and the effects on MRI parameters.