Cladribine tablets were associated with rapid onset of improvements in MRI outcomes in the ORACLE-MS trial (P3.2-061)

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 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. Disclosure: Dr. Scarberry has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, EMD Serono, & Genentech. Dr. Scarberry has received research support from Biogen, Teva, Mallinckrodt, Sanofi Genzyme, & EMD Serono. Dr. Damian has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono, Inc., Rockland, MA, USA (a business of Merck KGaA in Darmstadt, Germany). Dr. Hyvert has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono, Inc., Rockland, MA, USA (a business of Merck KGaA, Darmstadt, Germany). Dr. Dangond has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono, Inc. Dr. Lebson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono, Inc. Dr. Leist has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech, Biogen, EMD Serono, Teva, Sanofi-Genzyme, Bayer. Dr. Leist has received research support from Johnson and Johnson (Acelion); Novartis, Biogen, Chugai, Alkermes, Genentech,Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer and Teva Neuroscience.