Efficacy and Safety of 2 Doses of Ponesimod (10 and 20 mg o.d.): Interim Analysis of a Phase II Extension Trial in Relapsing-remitting Multiple Sclerosis (P3.398)

Objective: To compare efficacy and safety of ponesimod 20 mg (P20) vs. 10 mg (P10) in patients with relapsing-remitting multiple sclerosis (RRMS). Background: Once daily (o.d.) oral treatment with ponesimod, a novel selective S1P 1 receptor modulator, showed clinical benefits and reduced MRI activity in a phase II placebo-controlled trial in RRMS [i]. Patients in the ongoing extension of this trial are currently receiving 10 or 20 mg of ponesimod o.d. Design/Methods: Interim analysis of pooled data from patients randomized to P10 or P20 in the core trial or its extension was performed. Results: At 6 years, the Kaplan-Meier risk of 6-months confirmed disability accumulation was 29.6% and 16.4% for P10 and P20, respectively (relative risk reduction [RRR]: 49%; 95% CI: 8–72%; p = 0.024). The annualized confirmed relapse rate was 0.227 and 0.153 in the P10 and P20 arm, respectively (RRR: 32.5% [95% CI: −3.6–56.1%; p = 0.07]). The mean number of T1 gadolinium enhancing lesions per subject per scan was 1.371 and 0.768 in the P10 and P20 mg arm, respectively (RR: 44% [95% CI: 14.7–63.2%; p = 0.007]). The mean number of new or enlarging T2 lesions per subject per 24 weeks was 0.884 and 0.293 in the P10 and P20 arm, respectively (RRR: 66.9% [95% CI: 50.3–77.9%; p Conclusions: Ponesimod 20 mg o.d. compared to 10 mg o.d. has better clinical and MRI outcomes with similar safety profile. Study Supported by: Actelion Pharmaceuticals Ltd. Disclosure: Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Celgene, Merck, Novartis, Sanofi Genzyme, Teva. Dr. Achiron has nothing to disclose. Dr. Coyle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees (AbbVie, Accordant, Acorda, Bayer, Biogen Idec, Celgene, Genentech/Roche, Genzyme/Sanofi, Novartis, Serono, Teva). Dr. Coyle has received research support from Research support (Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, Novartis, Opexa). Dr. D9Ambrosio has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion. Dr. D9Ambrosio holds stock and/or stock options in Ju0026J and Idorsia. Dr. Eralinna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Novartis, Roche, Sanofi Genzyme, Teva. Dr. Hennessy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion. Dr. Lindenstroem has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion. Dr. Lycke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, Merck, Novartis, Teva. Dr. Lycke has received research support from Novartis, Teva. Dr. Izquierdo Ayuso has nothing to disclose. Dr. Pozzilli has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. Dr. Pozzilli has received research support from Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. Dr. Freedman has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen, Canada Innovation, Chugai, Clene Nanomedicine, EMD Canada, Hoffman-La Roche, Merck Serono, Novartis, Opexa, Sanofi Aventis, Sanofi Genzyme, and Teva.