Abstract Details

Title An Exploratory Analysis of Magnetic Resonance Imaging Outcomes in the DreaMS Trial: A Double-Blind, Placebo-Controlled, Phase 2, 26-Week Trial of a Selective Sphingosine 1-Phosphate Receptor Agonist ONO-4641 in Patients with Relapsing-Remitting Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) S31 - (-)

Poster/Presentation
Number 005

Objective

Background The DreaMS study assessed the efficacy and safety of ONO-4641, a selective sphingosine 1-phosphate (S1P) receptor-1 and -5 agonist, in patients with relapsing-remitting multiple sclerosis (RRMS). MRI outcomes were primarily lesion counts, analyzed using the Wilcoxon rank sum test. A further sensitivity analysis using a negative binomial (NB) model was prospectively planned. The NB model is better suited for the analysis of such zero-inflated, but highly skewed data, and it provides an estimate of the treatment effect and also allows for adjustment for covariates.

Design/Methods MRI outcomes were analyzed by an NB model adjusting for the number of lesions per patient at baseline.

Results Using NB analysis, the cumulative number of T1 gadolinium-enhancing lesions from Week 10 to 26 (primary endpoint) was significantly lower (p<0.0001) in all three active-treatment groups versus placebo (adjusted means: placebo, 5.65; 0.05 mg, 1.41; 0.10 mg, 0.57; 0.15 mg, 0.63; relative reduction [95% confidence interval {CI}] vs placebo: 0.05 mg 75% [57-85]; 0.10 mg, 90% [82-94]; 0.15 mg, 89% [80-94]). The cumulative number of new/enlarging T2 lesions was also significantly reduced (p<0.0001) with all three doses of ONO-4641 versus placebo (adjusted means: placebo, 8.01; 0.05 mg, 2.37; 0.10 mg, 1.68; 0.15 mg, 1.44; relative reduction [95% CI] vs placebo: 0.05 mg, 70% [54-81]; 0.10 mg, 79% [67-87]; 0.15 mg, 82% [72-89]).

Conclusions These findings confirm the robust, positive effect of ONO-4641 on MRI outcomes in patients with RRMS, as initially observed using the per-protocol planned primary analysis, and better characterize the dose-dependent effect of ONO-4641 on MRI outcomes.

Authors/Disclosures
PRESENTER	No disclosure on file
In Hye Jeong, MD (National Cancer Center)	No disclosure on file
Frauke Zipp, MD (University Medical Center Mainz)	Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Zipp has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Octapharma. Dr. Zipp 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. Zipp 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. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TEVA. The institution of Dr. Zipp has received research support from BMBF. The institution of Dr. Zipp has received research support from DFG. The institution of Dr. Zipp has received research support from PMSA. The institution of Dr. Zipp has received research support from Sanofi Genzyme. The institution of Dr. Zipp has received research support from UCB. The institution of Dr. Zipp has received research support from Eisai. The institution of Dr. Zipp has received research support from SK Life Science. The institution of Dr. Zipp has received research support from Abbott. The institution of Dr. Zipp has received research support from Actelion. The institution of Dr. Zipp has received research support from Bayer. The institution of Dr. Zipp has received research support from Servier. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with Novartis. Dr. Zipp has received personal compensation in the range of $0-$499 for serving as a Reviewer with Universite de Geneve. Dr. Zipp has received personal compensation in the range of $5,000-$9,999 for serving as a Reviewer with Oppenheim Förderpreis für Multiple Sklerose. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with EKFS. Dr. Zipp has a non-compensated relationship as a Associate Editor with Brain that is relevant to AAN interests or activities. Dr. Zipp has a non-compensated relationship as a Advisor with Science Translational Medicine that is relevant to AAN interests or activities.
Timothy L. Vollmer, MD, FAAN	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.
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.
Bryan R. Due, PhD (Ono Pharma USA)	No disclosure on file
Johan Van Beek, PhD	No disclosure on file
	No disclosure on file

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