Gilenya (Novartis)
0.5 mg capsules
Approved indication: multiple sclerosis
Australian Medicines Handbook section 16.6

Multiple sclerosis is thought to be an autoimmune disease. Some patients have therefore been treated with drugs such as glatiramer, interferon and natalizumab. A problem with these drugs is that they have to be injected. Fingolimod is an oral immunomodulator which has been approved for the treatment of relapsing–remitting multiple sclerosis, and secondary progressive multiple sclerosis with superimposed relapses.

Patients take fingolimod once a day. It is metabolised to its active form, fingolimod phosphate. This reduces the release of lymphocytes from lymphoid tissues which may prevent the cells from attacking the myelin sheaths of the nervous system.

Fingolimod is eliminated by metabolism with most of the metabolites being excreted in the urine. The terminal half-life is 6–9 days so it takes several weeks for a steady state to be reached.

In a phase II study, 281 patients with relapsing multiple sclerosis were randomised to take fingolimod 1.25 mg, 5 mg or placebo. After six months the mean cumulative number of lesions seen on MRI was 8.4, 5.7 and 14.8 respectively. The volume of the lesions was also significantly less in the patients given fingolimod. Although the study lacked the statistical power to confirm a treatment effect, there were more patients in the fingolimod group who were free of relapses than there were in the placebo group.1

The patients who completed the study could continue treatment. Those who had taken placebo were randomised to one of the fingolimod groups. After a further six months the number of lesions seen in the patients who had switched from placebo reduced, and remained low in those who continued fingolimod. At 12 months 65–67% of those who switched were free of relapse compared with 79% of those who took fingolimod continuously.1

A total of 189 patients completed a further extension of the study. After 24 months the number of lesions seen on MRI remained low. Between 12 months and 24 months the mean number of new lesions was less than one in all groups. Most (75–77%) of the patients who had been treated continuously remained relapse free.2

A larger placebo-controlled trial studied the effect of fingolimod 0.5 mg or 1.25 mg on disability and the rate of relapse. After 24 months, the annualised relapse rate was 0.16 in the 429 patients taking 1.25 mg, 0.18 in those taking 0.5 mg and 0.4 in those taking placebo. Approximately 70–75% of the fingolimod groups were relapse free for two years compared with 46% of the placebo group. The patients' disabilities did not progress in 82–83% of the fingolimod groups and 76% of the placebo group. These differences and the changes seen on MRI were statistically significant.3

Adverse events are more frequent with higher doses of fingolimod. In the large placebo-controlled trial 14.2% of patients taking 1.25 mg discontinued treatment because of adverse events compared with 7.5% of the 0.5 mg group and 7.7% of the placebo group.3As fingolimod reduces the peripheral lymphocyte count there is a potential increased risk of infection. The overall rate of infection is similar, but in one study lower respiratory tract infections were more common with fingolimod than with placebo.3As fingolimod is slowly excreted, it may take up to two months for lymphocyte counts to return to normal. The patient's immunity to organisms such as varicella should be checked before treatment begins. Liver function should also be checked as it is more frequently altered by fingolimod than by placebo.3The risk of adverse reactions may be greater in patients with hepatic impairment. Blood pressure should be monitored as hypertension can occur during treatment. Fingolimod also reduces the heart rate and can cause atrioventricular block.3Patients need to be observed for six hours after taking the first dose. Macular oedema may occur so patients also need ophthalmological assessments.3

To help establish its place in therapy, oral fingolimod has been compared to intramuscular interferon beta-1a. A total of 1292 patients with relapsing-remitting multiple sclerosis were randomised to receive daily fingolimod 0.5 mg or 1.25 mg, or weekly injections of interferon 30 microgram. After a year the rate of relapse was significantly lower in the fingolimod groups. Approximately 80–83% of these patients had no relapse compared with 69% of the interferon group. Although there were fewer new or enlarged lesions seen on MRI with fingolimod, there were no significant differences from interferon in the time to progression of disability. Fingolimod 1.25 mg and interferon had similar rates of adverse events, but fewer of the patients taking interferon discontinued treatments. The rates of infection were similar, but atrioventricular block and macular oedema only occurred in patients taking fingolimod. Skin cancers and hypertension were also more frequently found in the fingolimod groups.4

Fingolimod appears to have greater efficacy than interferon over a year, but multiple sclerosis is a long-term disease. Postmarketing studies will be needed to assess not only effectiveness, but also the emergence of any long-term adverse effects.

manufacturer provided the product information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

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