Abstract: Long-Term Efficacy and Safety of Siponimod in Active SPMS and Overall SPMS Populations: Expand Study Data up to 5 Years (2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers)

DMT15
Long-Term Efficacy and Safety of Siponimod in Active SPMS and Overall SPMS Populations: Expand Study Data up to 5 Years

Tuesday, October 26, 2021

Exhibit Hall (Rosen Shingle Creek)

Bruce A.C. Cree, MD, PhD, MAS , Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA

Gavin Giovannoni, MD, PhD , Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom

Ralf Gold, MD , Department of Neurology, St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany

Robert J. Fox, MD , Mellen Center for Treatment and Research in Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH

Patrick Vermersch, MD, PhD , Univ. Lille, Inserm U1172, CHU Lille, FHU Precise, Lille, France

Ralph H.B. Benedict, PhD , Jacobs Multiple Sclerosis Center, University at Buffalo, Buffalo, NY

Amit Bar-Or, MD , Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Nicolas Rouyrre, MSc , Novartis Pharma AG, Basel, Switzerland

Daniela Piani-Meier, PhD , Novartis Pharma AG, Basel, Switzerland

Shannon Ritter, MS , Novartis Pharmaceuticals Corporation, East Hanover, NJ

Ajay Kilaru, MBBS , Novartis Pharma AG, Basel, Switzerland

Frank Dahlke, MD , Novartis Pharma AG, Basel, Switzerland

Goeril Karlsson, PhD , Novartis Pharma AG, Basel, Switzerland

Ludwig Kappos, MD , Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland

Background: In the EXPAND Core study, siponimod significantly reduced the risk of 3-/6-months(m) confirmed disability progression (3m/6mCDP) and 6m confirmed ≥4-points clinically meaningful worsening on Symbol Digit Modalities Test (6mCW_SDMT) vs placebo in the active SPMS subgroup (aSPMS, presence of relapses 2 years before screening and/or ≥1 T1 gadolinium-enhancing lesion at baseline) and overall SPMS population.

Objectives: Assess long-term efficacy and safety of siponimod in aSPMS and overall SPMS population from the Core and Extension parts of EXPAND.

Methods: This analysis included Core and 36m extension data from all study participants who received ≥1 dose of siponimod 2 mg or placebo (cut-off 06Apr2019; total study duration of ≤5 years). Time-to-6mCDP by Expanded Disability Status Scale, time-to-6mCW_SDMT and annualized relapse rate (ARR) were assessed for the Continuous (siponimod in Core+Extension) and Switch (placebo in Core and open-label siponimod in Extension) groups. Safety was also evaluated.

Results: Of 1651 SPMS patients randomized in the EXPAND Core part, 1224 (74%) patients entered Extension (878 [72%] ongoing). Of 779 patients with aSPMS randomized in the Core part, 582 entered Extension. In the Continuous vs Switch group, 6mCDP risk was reduced by 29% (p=0.0044) and 22.3% (p=0.0026) in aSPMS and the overall population; time to reach the 25^th 6mCDP percentile was delayed by 78% and 54%, respectively. Time for 50% of patients to reach 6mCDP in aSPMS and the overall population was 48m and 51.7m respectively for Switch group. For the Continuous group, less than 50% reached 6mCDP. In the Continuous vs Switch group, 6mCW_SDMT risk was reduced by 33% (p=0.0018) and 23% (p=0.0047) in aSPMS and the overall population; time to reach the 25^th 6mCW percentile was delayed by 45% and 62%, respectively. Median time-to-6mCW_SDMT (55.5m) was reached only for the Switch group in the aSPMS cohort. ARR reduction was significant in the Continuous vs Switch group across aSPMS (39.7%; p=0.0023) and overall (52%; p<0.0001) populations. Incidence rates of adverse events/100 patient-years in both populations were consistent over the long-term period with no new safety findings observed.

Conclusions: The differences in sustained treatment effects (disability, relapse and cognitive processing speed) over the long-term period between Continuous siponimod and placebo-Switch groups highlight the benefit of early siponimod treatment initiation in SPMS. The safety profile remained favorable and consistent with previous reports.

DMT15 Long-Term Efficacy and Safety of Siponimod in Active SPMS and Overall SPMS Populations: Expand Study Data up to 5 Years

DMT15
Long-Term Efficacy and Safety of Siponimod in Active SPMS and Overall SPMS Populations: Expand Study Data up to 5 Years