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Abstract Details

Hepatic Safety of Ozanimod in Phase 3 Relapsing Multiple Sclerosis Trials
Multiple Sclerosis
MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)
221

Report hepatic safety data from ozanimod phase 3 RMS clinical trials.

Hepatic enzyme increases have been observed with other S1P modulators.
Compare ozanimod 0.92mg with IFNβ-1a 30µg/wk pooled data from SUNBEAM (NCT02294058; ≥12 months) and RADIANCE (NCT02047734; 24 months) trials. Liver enzymes were assessed at baseline, months 1 and 3, and every 3 months thereafter.
Mean (SD) exposure: ozanimod 0.92mg (n=882), 18.1 (6.0) months; IFNβ-1a (n=885), 17.8 (6.2) months. Postbaseline elevations in ALT ≥3× and ≥5× the upper limit of normal (ULN) occurred in 48/878 (5.5%) and 14/878 (1.6%) participants, respectively, on ozanimod 0.92mg, and 27/879 (3.1%) and 11/879 (1.3%) on IFNβ-1a. Upon repeat testing, ALT elevations ≥3×ULN and ≥5×ULN were confirmed in 18/878 (2.1%) and 4/878 (0.5%) participants, respectively, on ozanimod 0.92mg, and 12/879 (1.4%) and 7/879 (0.8%) on IFNβ-1a. AST elevations ≥3×ULN and ≥5×ULN occurred in 9/878 (1.0%) and 5/878 (0.6%) on ozanimod 0.92mg, and 19/879 (2.2%) and 10/879 (1.1%) on IFNβ-1a. Bilirubin elevations >2×ULN occurred in 14/878 (1.6%) on ozanimod 0.92mg and 2/879 (0.2%) on IFNβ-1a. Among participants with ALT ≥3×ULN, 93.8% and 96.3% of those on ozanimod 0.92mg and IFNβ-1a recovered to <3×ULN, predominantly while still receiving study drug (median time to recovery: ~2wk). Hepatic treatment-emergent adverse events (TEAEs) of hepatobiliary disorders and laboratory investigations occurred in 15 (1.7%) and 143 (16.2%) participants, respectively, on ozanimod 0.92mg, and 10 (1.1%) and 94 (10.6%) on IFNβ-1a; TEAEs of hepatobiliary disorders or investigations leading to discontinuation occurred in 2 (0.2%) and 10 (1.1%) participants on ozanimod 0.92mg, and 0 and 7 (0.8%) on IFNβ-1a. No severe drug-induced liver injury (DILI) occurred.

In phase 3 RMS trials, compared with IFNβ-1a, hepatic enzyme elevations ≥3×ULN and ≥5×ULN with ozanimod 0.92mg/d were low and confirmed infrequently; few participants discontinued treatment due to hepatic TEAEs. No cases of severe DILI were observed.
Authors/Disclosures

PRESENTER 		No disclosure on file
No disclosure on file
Amit Bar-Or, MD, FRCPC (University of Pennsylvania) Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty) Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
Eva Havrdova, MD (Neurologicka Klinika 1 LF UK) Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi.
James K. Sheffield, MD (Dianthus Therapeutics) Dr. Sheffield has received personal compensation for serving as an employee of BMS.
Neil Minton Neil Minton has received personal compensation for serving as an employee of Bristol Myers Squibb. Neil Minton has received stock or an ownership interest from Bristol Myers Squibb.
No disclosure on file
No disclosure on file
Diego Silva (Bristol-Myers Squibb Company) Diego Silva has received personal compensation for serving as an employee of BMS. Diego Silva has received stock or an ownership interest from BMS.
Jeffrey A. Cohen, MD (Cleveland Clinic) Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion.