Fingolimod Capsules (Gilenya™)
Fingolimod Capsules (Gilenya)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
The FDA has approved the first oral medication for the treatment of patients with relapsing forms of multiple sclerosis. Fingolimod is a sphingosine 1-phosphate receptor modulator that is believed to reduce migration of lymphocytes into the central nervous system. Fingolimod is marketed by Novartis as Gilenya.
Fingolimod is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.1
The recommended dose is 0.5 mg taken once daily. It may be taken without regard to meals.1 Fingolimod is available as 0.5 mg capsules.
Compared to interferon beta-1a, the annualized relapse rate was significantly lower with fingolimod.1,2
Fingolimod may decrease heart rate and slow atrioventricular conduction after the first dose. Patients should be observed for signs and symptoms of bradycardia for 6 hours after the first dose.1 The drug may also increase the risk for macular edema and infections, and may elevate liver transaminases. It may also decrease pulmonary function. Ophthalmologic evaluation should be done prior to initiation of therapy and at 3-4 months after initiation. EKG, CBC, liver transaminases, spirometry, and diffusion lung capacity for carbon monoxide should be evaluated as clinically indicated.
Fingolimod is metabolized to fingolimod-phosphate, which is active and has high affinity to sphingosine 1-phosphate receptors. This results in blocking the egress of lymphocytes from lymph nodes and ultimately reduces the number of lymphocytes in the systemic circulation to 20%-30% of baseline.1 The result is the reduction of migration of lymphocytes into the central nervous system. The efficacy of fingolimod was shown in two studies. The first study (FREDOM) involved MS patients (n = 1272) with relapsing-remitting multiple sclerosis (RRMS) and a score of 0 to 5.5 on the Expanded Disability Status Scale (EDSS), who had one or more relapses in the previous year or two or more in the previous 2 years, and who had not received interferon beta, glatiramer acetate, or natalizumab.1,3 Patients were randomized to fingolimod 0.5 mg or 1.25 mg daily, or placebo. The primary endpoint was the annualized relapse rate. At 24 months the annualized rate was 0.18, 0.16, and 0.4 for fingolimod 0.5 mg, 1.25 mg, and placebo, respectively. Both strengths of fingolimod were statistically significant from placebo (P < 0.001).
The second study (TRANSFORMS) was a comparison between fingolimod and intramuscular interferon beta-1a in subjects with RRMS (n = 1292) with inclusion criteria similar to study 1.1,2 However, prior interferon beta and glatiramer acetate use was permitted, but not natalizumab. Patients were randomized to either of the two doses of fingolimod or interferon beta-1 (30 mg IM once weekly). The duration was 12 months with a primary endpoint of annualized relapse rate. Secondary endpoints were the number of new or enlarged lesions on MRI at 12 months. The annualized rates were significantly lower for fingolimod (0.16 and 0.20) compared to interferon beta (0.33). MRI results were also similar to that of the primary endpoints. There were no differences in disease progression. Some adverse effects were more frequent with interferon; these included pyrexia (17.9% vs 4.2%), influenza-like illness (36.9% vs 3.5%), myalgia (10.2% vs 3.3%), and depression (7.4% vs 4.9%). Elevation of liver enzymes (6.5% vs 1.9%), bradycardia/AV block (0.6% vs 0%), and neoplasm (1.9% vs 0.2) were more frequent with fingolimod. The 1.25 mg dose of fingolimod was no more efficacious than the 0.5 mg dose, but was generally associated with a higher frequency of serious adverse events. There were two fatal infections (disseminated primary varicella zoster and herpes simplex encephalitis).
RRMS is the most common form of multiple sclerosis. Current FDA approved treatments include injectable forms of interferon beta-1a (intramuscular or subcutaneous administration), interferon beta-1b, glatiramer acetate, natalizumab, and mitoxantrone. Fingolimod is the first orally effective drug for RRMS and appears to be more effective than intramuscular interferon beta-1a. It provides an alternative for patients who have inadequate response or are intolerant of current agents. The long-term safety of fingolimod remains to be established. Fingolimod is currently in a phase III trial in patients with primary progressive MS.4
1. Gilenya Prescribing Information. East Hanover, NJ: Norvartis; September 2010.
2. Cohen JA, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010;362:402-415.
3. Kappos L, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010;362:387-401.
4. Pozzilli C, et al. Treating multiple sclerosis with fingolimod or intramuscular interferon. Expert Opin Pharmacother 2010;11:1957-1960.The FDA has approved the first oral medication for the treatment of patients with relapsing forms of multiple sclerosis.
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