Long-term Efficacy and Safety of Siponimod in Patients with SPMS: EXPAND Extension Analysis Up to 5 Years (4128)

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

Background: In the EXPAND-Core, siponimod showed significant reductions in confirmed disability progression (3-/6-month(m) CDP) and cognitive decline in typical SPMS patients.

Design/Methods: 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.

Results: 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 25^th 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 [0.65–0.92]), corresponding to a delay of 62% for the 25^th 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.

Conclusions: 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.

Disclosure: Dr. Kappos has received research support from Bayer, Biogen, Innosuisse, Novartis, the Swiss MS Society, the Swiss National Research Foundation, and the European Union.Dr. Giovannoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Actelion, Atara Biotherapeutics, Bayer, Biogen, Canbex Therapeutics, Five Prime Therapeutics, GSK, GW Pharmaceuticals, Merck, Merck Serono, Novartis, Oxford PharmaGenesis, Protein Discovery Laboratories, Roche, Sanofi Genzyme, Synthon, Teva, and UCB. Dr. Giovannoni has receive research support from AbbVie, Actelion, Atara Biotherapeutics, Bayer, Biogen, Canbex Therapeutics, Five Prime Therapeutics, GSK, GW Pharmaceuticals, Merck, Merck Serono, Novartis, Oxford PharmaGenesis, Protein Discovery Laboratories, Roche, Sanofi Genzyme, Synthon, Teva, and UCB.Dr. Gold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Diseases, Experimental Neurology and the Journal of Neuroimmunology. Dr. Gold has received research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis.Dr. Fox has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Robert Fox has received compensation for serving as a consultant or speaker from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, and Teva. He, or the institution he works for, has received research support from Novartis.. Dr. Fox has received research support from He, or the institution he works for, has received research support from Novartis..Dr. Vermersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Vermersch has received research support from Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva.Dr. Benedict has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ralph H. B. Benedict is on the speakers’ bureau for EMD Serono, and consults for Biogen Idec, Genentech, Roche, Sanofi/Genzyme, Takeda, NeuroCog Trials, and Novartis.. Dr. Benedict has received royalty, license fees, or contractual rights payments from Psychological Assessment Resources. Dr. Benedict has received research support from Ralph H. B. Benedict has received research support from Accorda, Novartis, Genzyme, Biogen Idec, and Mallinkrodt, and is on the speakers’ bureau for EMD Serono.. Amit Bar-Or has participated as a speaker in meetings sponsored by, and received consulting fees from, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, Janssen/Actelion, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme. Grant support from Janssen/Actelion, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme.Dr. Rouyrre has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG. Dr. Piani Meier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG, Basel, Switzerland. Dr. Ritter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharmaceuticals Corporation, NJ, USA. Dr. Kilaru has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG, Basel, Switzerland.. Dr. Dahlke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG, Basel, Switzerland. Dr. Karlsson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG, Basel, Switzerland. Dr. Cree has received personal compensation from Akili, Alexion, Atara, Biogen, EMD Serono, Novartis, TG Therapeutics.