Abstract Details

Title Long-Term Safety of Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: Results from Phase 3 FREEDOMS II Extension Study

Topic MS and Related Diseases

Presentation(s) P01 - (-)

Poster/Presentation
Number 165

Objective

Background BACKGROUND: In the 24-month, FREEDOMS II study, once daily, oral fingolimod (0.5mg or 1.25mg) was generally well tolerated in patients with relapsing-remitting multiple sclerosis.

Design/Methods DESIGN/METHODS: In the extension phase, fingolimod-treated patients continued with their assigned dose while placebo patients were re-randomized (1:1) to fingolimod 0.5mg/1.25mg (switch group: placebo-0.5mg and placebo-1.25mg). After protocol amendment, all patients received fingolimod 0.5 mg. Safety assessments included adverse events (AEs), serious AEs (SAEs), and laboratory evaluations; events occurring in the extension are presented.

Results RESULTS: 529/632 patients completed the extension study (83.7%). Withdrawal of consent and AEs were the main reasons for discontinuations (4.7% each). In both continuous and switch groups, AEs were reported in 85.3%-87.9% of patients. Placebo-1.25mg patients (11.4%) reported highest incidence of SAEs versus others (7.4%, 7.8% and 3.7% in the 1.25mg, 0.5mg and placebo-0.5mg). The 1.25mg (8.4%) patients reported highest AEs leading to study discontinuations versus others (4.8-7.5%). Across all groups serious infections were comparable (0.9-2%). One patient on 1.25mg reported severe herpes zoster. After first dose of fingolimod, placebo-0.5mg patients reported hypotension (n=1; SAE) and symptomatic bradycardia (n=2) and placebo-1.25mg patients reported first degree atrioventricular (AV) block, bradycardia and Mobitz type I second degree AV block (all SAEs and n=1). One patient each on placebo-1.25mg and placebo-0.5mg reported confirmed macular edema. Patients on 1.25mg (n=2) and 0.5mg (n=1) reported squamous cell carcinoma. One patient on 0.5mg reported basal cell carcinoma. Placebo-1.25mg patients reported highest (6.7%) increase in alanine aminotransferase enzyme (>3xULN) versus others (1.5%, 4.6% and 4.7% in the 1.25mg, 0.5mg and placebo-0.5mg).

Conclusions CONCLUSIONS: The long-term safety results of FREEDOMS II extension study were generally consistent with previous fingolimod studies. Switching therapy from placebo to fingolimod after 24 months identified no unexpected safety concerns.

Authors/Disclosures
Timothy L. Vollmer, MD, FAAN PRESENTER	The institution of Dr. Vollmer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen IDEC. The institution of Dr. Vollmer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siranax. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers Squib. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bios. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Vollmer has received research support from Rocky Mountain MS Center. The institution of Dr. Vollmer has received research support from Biogen. The institution of Dr. Vollmer has received research support from Actelion. The institution of Dr. Vollmer has received research support from Genentech/Roche. The institution of Dr. Vollmer has received research support from Anokion. The institution of Dr. Vollmer has received research support from TG Therapeutics.
Douglas R. Jeffery, MD, PhD (Lake Norman Neurology At Piedmont Health Care)	No disclosure on file
Douglas S. Goodin, MD (Univ of Calif at San Francisco)	No disclosure on file
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
Nicholas S. Abend, MD, FAAN (Children's Hospital of Philadelphia)	Dr. Abend has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Epilepsy Foundation. The institution of Dr. Abend has received research support from NIH. The institution of Dr. Abend has received research support from PCORI. Dr. Abend has received publishing royalties from a publication relating to health care.
Fred D. Lublin, MD, FAAN (Icahn School of Medicine At Mount Sinai)	Dr. Lublin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche/Genentech. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurogene. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medimmune/Viela Bio/Horizon. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Receptos/Celgene/BMS. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Labcorp. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuralight. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Entelexo. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avotres. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Lublin has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Lublin has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Multiple entities. Dr. Lublin has stock in Avotres. Dr. Lublin has stock in Neuralight. The institution of Dr. Lublin has received research support from Brainstorm. The institution of Dr. Lublin has received research support from biogen. The institution of Dr. Lublin has received research support from NIH.
Ernst-Wilhelm Radue, MD (Medical Image Analysis Center)	Dr. Radue has nothing to disclose.
Kottil W. Rammohan, MD (University of Miami)	Dr. Rammohan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Rammohan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Rammohan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Rammohan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Rammohan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Rammohan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. The institution of Dr. Rammohan has received research support from Genentech. The institution of Dr. Rammohan has received research support from Genzyme. The institution of Dr. Rammohan has received research support from EMD Serono. The institution of Dr. Rammohan has received research support from Alexion.
Anthony Reder, MD (University of Chicago)	Dr. Reder has nothing to disclose.
Mark Agius, MD (Barrow Neurological Institute Dept of Neurology)	No disclosure on file
Tracy E. Stites, PhD	Dr. Stites has received personal compensation for serving as an employee of Novartis Pharmaceuticals. Dr. Stites has received stock or an ownership interest from Novartis Pharmaceuticals.
Bingbing Li	Bingbing Li has received personal compensation for serving as an employee of Novartis.
Linda Cappiello (Novartis)	No disclosure on file
	No disclosure on file
Peter A. Calabresi, MD, FAAN (Johns Hopkins University)	Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. An immediate family member of Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MyMD. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Myelin Repair Foundation. The institution of Dr. Calabresi has received research support from Genentech. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME.

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