Today in the office I had my first patient come in who was taking Gilenya, the first oral disease modifying medication for multiple sclerosis. Gilenya, generic name fingolimid, was approved by the FDA for treatment of relapsing multiple sclerosis on Sept. 22, 2010 and brought to market by Novartis. My patient decided to change from her prior medication Tysabri because getting to her specialist’s office in Seattle for an IV infusion on the Tysabri every 4 weeks was difficult and for her taking a daily oral medication was a much better option. Many patients with the relapsing type of MS need help with transportation to doctors appointments, and so an oral medication may be a major advantage.
Gilenya is the first medication in a class of drugs called sphingosine 1-phosphate receptor modulators, and it is felt to preventing some types of lymphocytes from leaving the lymph nodes and in that way keeping them from crossing into the brain and leading to inflammatory damage to nerve cells in the brain. Two different studies reported in the NEJM looked at Gilenya, both of which appear promising. In the FREEDOMS study over 2 years Gilenya reduced relapses of MS by 54% and reduced progression of disability by 30% compared to placebo. In another study called the TRANSFORMS study, Gilenya was compared to Avonex (interferon beta-1a) and over a 1 year timeframe reduced relapses by 52%$ compared to Avonex, and reduced the number of new sclerotic plaques seen on MRI in the brain compared to Avenex (1.6 vs 2.6 new lesions on T2 weighted MRI imaging).
Overall Gilenya sounds promising and convenient for patients with the relapsing form of multiple sclerosis, and may become more popular as physicians gain more experience with this medication. The initial studies of efficacy look good, but the indication only for the relapsing type of MS makes it appropriate at this time only for this sub-set of MS patients.
There are some quite unusual aspects of therapy with Gilenya. First is that the same fixed dose is used for all patients. Gilenya 0.5 mg once daily is the only approved dose. Second is that the first dose of Gilenya can lead to severe bradycardia (slow heart rate) due to atrioventricular block. The first dose is to be given in the physician’s office, and the patient is to be observed for 6 hours for bradycardia. Patients with cardiac risk factors, using heart medications, or who have slow or irregular heart rate on exam should have an EKG prior to starting Gilenya. If a patient has not had chicken pox they should have antibody testing done to assure varicella immunity. If immunity is not found they should consider chickenpox vaccination because chicken pox infection while on Gilenya can be very severe.
Gilenya has several somewhat unusual and potentially severe side effects other than the first dose bradycardia. These include macular edema, swelling of the area in the center of the retina of the eye where the maximum vision acuity is located. Reduction in lymphocyte count can lead to risk of infections. Severe hepatotoxicity and shortness of breath are additional unusual Gilenya side effects.
Gilenya has extensive liver metabolism using the CYP-450 pathway including many of the common pathways, and so the list of potential drug interactions is extensive. Patients should not receive live virus vaccines while on Gilenya, including the live intranasal influenza vaccination and MMR vaccine. Special care is needed with any medications that can lead to bradycardia including beta-blockers, several classes of antiarrythmic medications, digoxin and the calcium channel blockers.
It will be interesting to see how much of the market for aggressive disease modifying treatment of MS Gilenya gets used for as experience with the drug grows.