Onset of Action of Ozanimod for MRI Outcomes in Patients With Relapsing Multiple Sclerosis (4265)

Objective: To estimate the onset of action of ozanimod, we analyzed monthly MRI scans in a 24-week, phase 2, randomized, double-blind, placebo-controlled study (RADIANCE [NCT01628393]) of ozanimod 0.46 and 0.92 mg/day in relapsing multiple sclerosis (RMS; N=258).

Background: Knowledge of the onset of action by magnetic resonance imaging (MRI) for disease-modifying therapies in RMS is important for treatment monitoring.

Design/Methods: MRI scans were acquired at baseline, W8, W12, W16, W20, and W24. In this post hoc analysis, onset of action was estimated for reduction in number of gadolinium-enhancing (GdE) lesions (primary outcome), number of new/enlarging T2 lesions, T2 lesion volume, number of new un-enhancing T1 lesions (black holes), and whole brain atrophy rate (all secondary outcomes). Onset of action was defined as the earliest time point at which a nominally significant difference (P<0.05) in the rate ratio of the least square means (LSM) and 95% confidence intervals (CIs) between ozanimod 0.92 mg and placebo occurred and was sustained.

Results: Nominally significant reductions in number of GdE and new/enlarging T2 lesions were observed beginning at W8 for ozanimod 0.92 mg vs placebo; CIs for LSM number of GdE and new/enlarging T2 lesions did not overlap from W12 onward. For new black holes, a nominally significant difference was observed beginning at W12 for ozanimod 0.92 mg vs placebo; however, CIs for LSMs, which were wide in the placebo group, overlapped at all time points except W20. No obvious changes were observed for T2 lesion volume or whole brain atrophy over 24 weeks in this small sample.

Conclusions: Onset of action of ozanimod 0.92 mg based on GdE and new/enlarging T2 MRI lesion activity in this phase 2 study was detected as early as W8, the earliest available MRI time point, with complete separation from placebo beginning at W12.

Disclosure: Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for La revue des microbiotes. The institution of Patrick Vermersch has received research support from Roche. The institution of Patrick Vermersch has received research support from Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GENeuro. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Receptos/Celgene. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received stock or an ownership interest from NeuroRx. The institution of Dr. Arnold has received research support from Novartis. The institution of Dr. Arnold has received research support from Immunotec. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Adamas. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 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 MedDay. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Giancarlo Comi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono SpA. Giancarlo Comi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Celgene Group. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Almirall. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for F. Hoffman-La Roche. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Giancarlo Comi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono SpA. Giancarlo Comi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene Group. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffman-La Roche. Giancarlo Comi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Almirall. 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 Janssen/Actelion. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara Biotherapeutics. 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 BMS. 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 on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. 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. The institution of Dr. Bar-Or has received research support from Merck/EMD Serono. Chahin Pachai has nothing to disclose. Hongjuan Liu has received personal compensation for serving as an employee of BMS. Dr. Sheffield has received personal compensation for serving as an employee of BMS. Diego Silva has received personal compensation for serving as an employee of BMS. Diego Silva has received stock or an ownership interest from BMS. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Krzystof Selmaj has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mylan. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche . Krzystof Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis.