Long-term Efficacy and Safety of Siponimod in Patients with SPMS: EXPAND Extension Analysis Up to 5 Years
Ludwig Kappos1, Gavin Giovannoni2, Ralf Gold3, Robert J. Fox4, Patrick Vermersch5, Ralph H.B. Benedict6, Amit Bar-Or7, Nicolas Rouyrre8, Daniela Piani Meier8, Shannon Ritter9, Ajay Kilaru8, Frank Dahlke8, Goeril Karlsson8, Bruce A.C. Cree10
1Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland, 2Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 3Department of Neurology, St Josef-Hospital/Ruhr-University Bochum, Bochum, Germany, 4Mellen Center for Treatment and Research in Multiple Sclerosis, Neurological Institute, Cleveland, OH, USA, 5Department of Neurology, University of Lille, CHU Lille, LIRIC-U995, FHU-Imminent, Lille, France, 6Department of Neurology, University at Buffalo, Buffalo, NY, USA, 7Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, 8Novartis Pharma AG, Basel, Switzerland, 9Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 10Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA

To assess the long-term efficacy and safety of siponimod in patients with SPMS from the Core and Extension parts of the EXPAND study.

In the EXPAND-Core, siponimod showed significant reductions in confirmed disability progression (3-/6-month(m) CDP) and cognitive decline in typical SPMS patients.
This analysis included patients who received 1 dose of randomized treatment (Siponimod 2mg/placebo; 36m Extension data cut-off [April-2019]; total study duration 5 years). Efficacy analyses included time-to-3m/6mCDP on Expanded Disability Status Scale, time-to-6m confirmed worsening (6mCW: 4 points in Symbol Digit Modalities Test) and annualized relapse rate (ARR) for continuous siponimod group (CSG: siponimod in Core + Extension) and switch group (PSG: placebo in Core/switched to siponimod in Extension). Safety was also evaluated.
Of the 1224 (74% of 1651 randomized) patients entering the Extension, 878 (72%) were ongoing. Patients in CSG were less likely to experience 3mCDP (p=0.0064) and 6mCDP (p=0.0048) versus PSG. Time to 6mCDP was prolonged, corresponding to a delay of 54% for the 25th percentile (21.0 vs. 13.6 months) in the CSG versus PSG. Median time-to-6mCDP was not reached for CSG (PSG: 51.7 months). Time-to-6mCW on SDMT was delayed in CSG versus PSG (p=0.0014). Risk of worsening on the SDMT was reduced by 23% (0.77 [0.650.92]), corresponding to a delay of 62% for the 25th percentile (CSG vs. PSG: 29.6 vs. 18.3 months). A reduction in ARR by 52% was observed in the CSG versus PSG (0.054 vs. 0.097; p<0.0001). Incidence rates of AEs/100 patient-years in the long-term follow up were consistent with the controlled treatment period; no new safety findings were observed.

Benefits of CSG over PSG gained during the controlled period are sustained for up to 5 years, suggesting a continuous effect of siponimod and underlining the advantages of early treatment initiation with siponimod.