Efficacy Outcome Measures of Oral Ponesimod Compared to Teriflunomide in Patients with Relapsing Multiple Sclerosis: Results of the Randomized, Active-Controlled, Double-Blind, Parallel-Group Phase 3 OPTIMUM Study

Objective: Compare efficacy of ponesimod versus teriflunomide, an approved first-line oral medication, in patients with relapsing multiple sclerosis (RMS). Background: Ponesimod, an orally active, highly selective and reversible modulator of sphingosphine-1 phosphate (S1P1) receptor, blocks lymphocyte migration out of lymphoid tissue, thereby reducing peripheral lymphocyte counts and preventing lymphocyte recruitment to inflammation sites. Design/Methods: OPTIMUM, a multicenter, randomized, double-blind active-controlled superiority phase 3 study (NCT02425644), enrolled adults (18–55 years) with established MS, relapsing course from onset, and expanded disability status scale (EDSS) score of 0–5.5. Patients were randomized (1:1) to ponesimod 20 mg or teriflunomide 14 mg once-daily for 108 weeks. Primary efficacy endpoint was annualized relapse rate (ARR); secondary endpoints included fatigue-related symptoms: fatigue symptom and impact questionnaire-RMS [FSIQ-RMS], combined unique active lesions per year [CUALs], time to 12-week and 24-week confirmed disability accumulation [CDA]; exploratory endpoint percent change in brain volume, and no evidence of disease activity (NEDA-3) status. Results: Of 1133 randomized patients, 86.9% completed the study. The respective ponesimod versus teriflunomide findings were: ARR 0.202 versus 0.290 (relative rate reduction [RRR]:30.5%; p=0.0003), mean change from baseline in FSIQ-RMS weekly symptoms score to Week 108 was −0.01 versus 3.57 (p=0.0019); mean number of CUALs per year on MRI was 1.405 versus 3.164 (RRR: 56%, p Conclusions: Ponesimod was superior to teriflunomide on ARR, fatigue symptoms, MRI activity, brain atrophy and NEDA with no significant difference on 12-week and 24-week CDA estimates. Disclosure: 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. Kappos has received research support from Bayer, Biogen, Innosuisse, Novartis, the Swiss MS Society, the Swiss National Research Foundation, and the European Union.Dr. Burcklen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson \u0026 Johnson. Dr. Burcklen has received compensation for serving on the Board of Directors of Johnson \u0026 Johnson. Dr. Freedman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen Idec, Chugai, Clene Nanomedicine, EMD Serono Canada, Genzyme, Merck Serono, Novartis, F. Hoffmann-La Roche Ltd, Sanofi-Aventis and Teva Canada Innovation. Dr. Freedman has received compensation for serving on the Board of Directors of Actelion, Bayer Healthcare, Biogen Idec, Clene Nanomedicine, F. Hoffmann-La Roche Ltd, Merck Serono, MedDay Pharmaceuticals, Novartis and Sanofi-Aventis. Dr. Freedman has received research support from Genzyme Canada. Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Celgene Corporation, Merck, Novartis, Roche, Sanofi, and Teva. Dr. Havrdova has received research support from Czech Ministry of Education, project PROGRES Q27/LF1.Dr. Hennessy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson \u0026 Johnson. Dr. Hennessy has received compensation for serving on the Board of Directors of Johnson \u0026 Johnson, Novo Nordisk, Arena Pharmaceuticals, and Galapagos. Dr. Hohlfeld has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. Dr. Hohlfeld has received research support from Biogen, Genzyme-Sanofi, Novartis, and Roche. Dr. Lublin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen; EMD Serono; Novartis; Teva; Actelion; Sanofi/Genzyme; Acorda; Roche/Genentech; MedImmune; Receptos/Celgene; Forward Pharma; TG Therapeutics; Abbvie; Regeneron; Medday; Atara Biotherapeutics; Polpharma; Mapi Pharma; Innate Immunotherapeutics; Apito. Dr. Lublin has received personal compensation in an editorial capacity for Multiple Sclerosis and Related Disorders- Co-Chief Editor. Dr. Lublin has received research support from Acorda Therapeutics, Biogen Idec, Genzyme, National MS Society, Novartis, Sanofi, Teva Neuroscience. Dr. Montalban has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Alexion, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Hoffmann-La Roche, Immunic AG, Medday, Medscape, Merck, Mylan, Nervgen, Novartis, Sanofi-Genzyme, Teva Pharmaceutical and TG Therapeutics. Dr. Montalban has received research support from Abbvie, Biogen, Hoffmann-La Roche, Medday, Merck, Novartis, Sanofi-Genzyme and Teva Pharmaceutical.Dr. Pozzilli has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Served on scientific advisory boards for Novartis, Merck, Biogen, Sanofi, Genzyme, Teva, Actelion and funding for travel and speaker honoraria from Biogen, Teva, Sanofi Genzyme, Actelion and Novartis. Dr. Pozzilli has received research support from Biogen, Teva, Novartis and Genzyme. Dr. Scherz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson \u0026 Johnson and a former employee of Novartis Pharma AG. Dr. Scherz has received compensation for serving on the Board of Directors of Johnson \u0026 Johnson. Dr. Linscheid has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with employee of Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson \u0026 Johnson.. Dr. Pirozek-Lawniczek has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with are employee of Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson \u0026 Johnson.. Dr. Kracker has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with employee of Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson \u0026 Johnson. Dr. Sprenger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with I did not receive any personal compensation. My employer received compensation for speaking, advisory board/consulting activities from: Actelion, Lilly, Roche, Novartis, Sanofi Genzyme and Teva..