Long-Term Safety Of Fingolimod: Updated Integrated Safety Analyses

Background: Previous clinical trial data show that fingolimod 0.5 mg, a once-daily, oral therapy approved for relapsing forms of multiple sclerosis (MS), has a manageable safety profile; label requirements for treatment initiation monitoring were recently updated.

Objectives: To report updated integrated safety results from fingolimod phase 2 and 3 studies.

Methods: Safety data for fingolimod 0.5 and 1.25 mg from phase 3 studies (FREEDOMS and FREEDOMS II, both 24 months vs placebo [PBO]; TRANSFORMS, 12 months vs interferon beta [IFNβ]–1a intramuscular [IM]) and from a phase 2 study (6 months) were pooled (fingolimod 0.5 mg, n=1212; fingolimod 1.25 mg, n=1313; PBO, n=866; IFNβ-1a IM, n=431).

Results: Discontinuations were more often related to adverse events (AEs) with fingolimod (5.4%–8.3%) and unsatisfactory therapeutic effect with PBO (8.0%). The proportion of patients with AEs were similar across groups (0.5 mg, 92.6%; 1.25 mg, 93.1%; PBO, 93.2%; IFNβ-1a IM, 91.9%) and serious AEs (as of October 31, 2011) were similar with fingolimod (0.5 mg, 10.5%; 1.25 mg, 11.6%) and PBO (12.2%); rates of infection AEs (51.0%–67.9%) and infection serious AEs (1.4%–2.0%) were also similar across groups. AEs of interest reported more frequently with fingolimod included: hypertension (0.5 mg, 6.5%; 1.25 mg, 7.8%; PBO, 3.3%; IFNβ-1a IM, 2.1%), liver transaminase elevations ≥3-fold the upper limit of normal (8.0%, 9.7%, 1.9%, 2.3%, respectively), bradycardia (1.0%, 2.3%, 0.6%, 0.5%), macular edema (0.4%, 1.3%, 0.4%, 0.2%) and 2nd-degree atrioventricular block (0.1%, 0.5%, 0.2%, 0%); few patients across treatment groups had malignant neoplasms.

Conclusions: Safety data from >3500 patients are consistent with the established profile of fingolimod, with no evidence in this combined clinical trial population of increased risk of infections, malignancies, or serious cardiovascular events with fingolimod vs PBO or IFNβ-1a IM.