The First FDA-Approved Oral Drug for Multiple Sclerosis: Fingolimod

Abstract

Disease-modifying drugs (DMDs) are being used in multiple sclerosis (MS) for the last 20 years. Until recently, only interferon beta and glatiramer acetate preparations were available, which are administered by repetitive injections. In the last quarter of 2010, the USA Food and Drug Administration (FDA) approved the first oral DMD, fingolimod. Fingolimod is a modulator of sphingosine-1 phosphate (SIP) receptors which are present in many tissues such as neural cells and lymphocytes. By inhibiting the S1P signalling which is necessary for lymphocytes to leave the lymph nodes, it traps lymphocytes within the lymph nodes causing lymphopenia. However, since it does not harm the lymphocytes, this lymphophenia is quickly reversible after the drug withdrawal. Both preclinical studies and Phase II and Phase Ill studies carried out in patients with relapsing MS have yielded promising results. In the Phase III trials, fingolimod was effective both against placebo and weekly interferon beta-1a injections in preventing relapses and lesion load accumulation. Phase II and Phase III studies showed that fingolimod has a favorable safety profile; long-term safety needs to be shown in long-term follow up-studies. (Archives of Neuropsychiatry 2011; 48 Supplement 2:64-6)