Fingolimod in relapsing multiple sclerosis: An integrated analysis of safety findings

Ludwig Kappos; Jeffrey Cohen; William Collins; Ana de Vera; Lixin Zhang-Auberson; Shannon Ritter; Philipp von Rosenstiel; Gordon Francis

doi:10.1016/j.msard.2014.03.002

Fingolimod in relapsing multiple sclerosis: An integrated analysis of safety findings

Mult Scler Relat Disord. 2014 Jul;3(4):494-504. doi: 10.1016/j.msard.2014.03.002. Epub 2014 Mar 25.

Authors

Ludwig Kappos¹, Jeffrey Cohen², William Collins³, Ana de Vera³, Lixin Zhang-Auberson³, Shannon Ritter⁴, Philipp von Rosenstiel³, Gordon Francis⁴

Affiliations

¹ Neurology, Department of Medicine, Clinical Research and Biomedicine, University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland. Electronic address: ludwig.kappos@usb.ch.
² Neurological Institute, The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
³ Novartis Pharma AG, CH-4056 Basel, Switzerland.
⁴ Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07849-1080, USA.

PMID: 25877062
DOI: 10.1016/j.msard.2014.03.002

Abstract

Background: Fingolimod 0.5mg once daily is the first approved oral therapy for relapsing multiple sclerosis (MS).

Objective: To report integrated long-term safety data from phase 2/3 fingolimod studies.

Methods: Descriptive safety data are reported from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study, a 24-month, randomized, double-blind study comparing fingolimod 0.5mg and 1.25mg with placebo, and an All Studies group (patients who received fingolimod 0.5mg (n=1640) or 1.25-0.5mg (n=1776) in phase 2/3 studies and associated extensions). Relevant post-marketing experience, up to December 2011, is included.

Results: The incidence of adverse events (AEs) and serious AEs (SAEs) was similar with fingolimod and placebo in FREEDOMS. In the All Studies group, fingolimod 0.5mg was associated with transient, rarely symptomatic (0.5%), bradycardia and second-degree atrioventricular block on treatment initiation, minor blood pressure increases, frequent (9%) but generally asymptomatic liver enzyme elevations, and macular oedema (0.4%). The incidences of infections (including serious and herpes infections), malignancies, SAEs and treatment discontinuations due to AEs were similar with fingolimod 0.5mg and placebo.

Conclusion: The safety profile of fingolimod has been well characterized in this large combined trial population. Although infrequent SAEs can occur, there is no increased risk of infections, malignancies or serious cardiovascular events versus placebo.

Keywords: Adverse events; Cardiovascular events; Fingolimod; Multiple sclerosis; Pooled analysis; Safety.