Cardiac Safety of Fingolimod 0.5 mg during the First Dose Observation in 4-Month, Open-Label, Multi-Center FIRST Study in Patients with Relapsing MS (S41.003)

Objective: To report the safety results of fingolimod 0.5 mg focusing on cardiac events during the first dose observation in relapsing MS patients both without cardiac risk factors and with cardiac conditions not included in fingolimod clinical trials. Background Fingolimod (FTY720) is an S1PR modulator approved for the treatment of relapsing MS. The initiation of fingolimod treatment results in generally asymptomatic and transient bradycardia and may be associated with atrioventricular blocks (AVB). Prescribing information recommends 6 hours on-site observation for signs and symptoms of bradycardia. Design/Methods: 2417 patients were enrolled. Preliminary results are reported for 2289 patients. Unless patients met pre-defined cardiac risk criteria the first dose administration was permitted off-site. Heart rate and ECG abnormalities were assessed by ambulatory Holter-ECG for 24 hours at screening and for 6 hours after administration of the first dose. Results: In the post-dose Holter ECGs the incidence of Mobitz I second degree AVBs was 1.4% and the incidence of 2:1 AVBs was 0.5%. One patient had a finding of >3 sec pause in both screening and post dose Holter-ECG. Incidence of conduction abnormalities was similar in patients monitored on-site (n=1162) and off-site (n=1127) and in patients with or without cardiac risks. One patient discontinued study drug due to the second degree AVB. No patient had a HR Conclusions: Overall incidence of AVBs on Holter-ECGs was low, irrespective of on- or off-site first dose administration or the presence of potential cardiac risk factors. These results are similar to those observed in fingolimod trials and confirm the benign nature of the cardiac effects of treatment initiation with fingolimod. Supported by: Novartis Pharma AG, Basel, Switzerland. Disclosure: Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. Dr. Kappos has received research support from Acorda Therapeutics, Actelion, Allozyne, BaroFold, Inc., Bayer Pharmaceuticals Corporation, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc, Elan Corporation, Genmab, GlaxoSmithKline, Inc., Glenmark Pharma, Merck Serono, MediciNova, Novartis, Sanofi-Aventis Pharmaceuticals, Santhera Pharmaceuticals, Shire, Roche Diagnostics, Teva Neuroscience, UCB Pharma, Pfizer Inc, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis and Roche Research Foundations. Dr. Palace has received personal compensation for activities with Teva Neuroscience, Biogen Idec, Merck Serono, and Bayer Schering Pharma. Dr. Palace has received research support from GlaxoSmithKline, Inc. Dr. Gottschalk has received personal compensation for activities with Novartis as an employee. Dr. Bijarnia has received personal compensation for activities with Novartis Healthcare Pvt Ltd as an employee. Dr. Keil has received personal compensation for activities with Novartis as an employee. Dr. Tomic has received personal compensation for activities with Novartis as an employee. Dr. von Rosenstiel has received personal compensation for activities with Novartis Pharma AG. Dr. von Rosenstiel holds stock and/or stock options in Novartis Pharma AG, which sponsored research in which Dr. von Rosenstiel was involved as an investigator. Dr. Gold has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Teva Neuroscience. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Gold has received (royalty or license fee or contractual rights) payments from Biogen Idec. Dr. Gold has received research support from Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Novartis and Teva Neuroscience.