Abstract Details

Title Cladribine tablets were associated with rapid onset of improvements in MRI outcomes in the ORACLE-MS trial

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-061

Objective To analyze the timing of effects of cladribine tablets on MRI outcomes in ORACLE-MS.

Background The Phase 3 randomized, placebo-controlled 96-week ORACLE-MS trial in 616 subjects with a first demyelinating event at high risk of converting to multiple sclerosis, demonstrated that cladribine tablets 10 mg (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years) significantly delayed the time to conversion to clinically definite multiple sclerosis (CDMS), and reduced the number of new or persisting T1 gadolinium-enhancing (T1 Gd+), new/enlarged or active T2 and combined unique active (CUA) lesions.

Design/Methods MRI scans were performed at screening and every 12 weeks, for those not converting to CDMS during the study. MRI-based endpoints were analyzed using analysis of covariance (ANCOVA) and negative binomial models. The temporal effects of the first yearly treatment course of cladribine tablets (CT) and placebo on T1 Gd+, active T2, and CUA lesions will be presented graphically.

Results Over 96 weeks, the reduction in mean T1 Gd+, active T2, or CUA lesion number per patient per scan was nominally significantly greater for CT compared with placebo (p<0.0001). An early change in Gd+ lesion volume was also found (change from baseline at Week 13: CT, -155.73 mm³; placebo, -14.76 mm³). Similarly, there were comparatively larger reductions in mean active T2 and CUA lesion numbers with CT at Week 13 compared with placebo (active T2: CT, -1.25; placebo, -1.43; CUA: CT, -1.56; placebo, -2.41). The mean number of T1 Gd+ lesions at 13 weeks following CT was 0.37 compared with 1.0 with placebo.

Conclusions These MRI data from ORACLE-MS in subjects with a first demyelinating event at high risk of converting to CDMS suggest the first yearly treatment course of cladribine tablets has a rapid onset of action, with beneficial treatment effects on active lesion number and volume evident within 13 weeks.

Authors/Disclosures
Susan L. Scarberry, MD, FAAN (Sanford Health) PRESENTER	Dr. Scarberry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Scarberry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich. Dr. Scarberry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenix. Dr. Scarberry has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Scarberry has received research support from Sanofi Genzyme.
	No disclosure on file
Yann Hyvert, PhD (Merck Healthcare KGaA)	Dr. Hyvert has received personal compensation for serving as an employee of The healthcare business of Merck KGaA, Darmstadt, Germany. An immediate family member of Dr. Hyvert has received personal compensation for serving as an employee of The healthcare business of Merck KGaA, Darmstadt, Germany.
Fernando Dangond, MD, FAAN	Dr. Dangond has received personal compensation in the range of $1,000,000+ for serving as a Head, Global Clinical Development (employee for 12 years) with EMD Serono.
Lori Lebson, PhD	No disclosure on file
Thomas Leist, MD, PhD, FAAN (Thomas Jefferson University)	Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Leist has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Seono. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Wittness with DHHS HRSA.

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