Abstract: P1151
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Once daily (o.d.) oral treatment with ponesimod 10, 20 or 40 mg, a novel selective S1P1 receptor modulator, significantly reduced the number of new T1 gadolinium-enhancing (Gd+) lesions and showed clinical benefits in a phase II placebo-controlled trial in relapsing-remitting multiple sclerosis (RRMS)[i]. Patients in the ongoing extension of this trial are currently receiving 10 or 20 mg of ponesimod o.d. Objectives: To compare efficacy and safety of ponesimod 20 mg (P20) vs. 10 mg (P10). Methods: Interim analysis of pooled data from patients randomized to ponesimod 10 or 20 mg (but not 40 mg) in the phase II trial or its extension: cut-off date 1 September 2016. Efficacy outcomes included 6-month confirmed disability accumulation (6 m-CDA), annualized relapse rate (ARR), mean number of T1 Gd+ lesions, and new/enlarging T2 lesions. Safety outcomes included frequency of all adverse events (AEs), serious AEs, and AEs leading to trial treatment discontinuation. A negative binomial model was used to analyse ARR and MRI lesion endpoints, and a Cox's proportional hazards model for 6 m-CDA. Results: Cumulative exposures to P10 and P20 were 613.8 and 615.9 years, respectively. At 6 years, the Kaplan-Meier risks of 6 m-CDA were 29.6% and 16.4% for P10 and P20, respectively, corresponding to a 49% (95% confidence interval [CI]: 8-72%; p=0.024) relative reduction (RR) in the P20 arm compared to the P10 arm. The ARR for confirmed relapses was 0.227 and 0.153 with P10 and P20, respectively (RR for P20 arm: 32.5% [95% CI: -3.6-56.1%; p=0.07]). For all relapses (i.e., confirmed and unconfirmed), the RR in the P20 arm was 33.5% (95% CI: 1.2-55.3%; p=0.043). The mean number of T1 Gd+ lesions per subject per scan was 1.371 and 0.768 with P10 and P20 mg, respectively (RR in the P20 arm: 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 with P10 and P20, respectively (RR in the P20 arm: 66.9% [95% CI: 50.3-77.9%; p< 0.0001]). The proportions (%) of P10 and P20 patients with all AEs, serious AEs, and AEs leading to treatment discontinuation were 94.2 vs. 91.0, 15.1 vs.13.8, and 12.2 vs.10.3, respectively. Conclusion: The pooled data from the phase II trial and its ongoing extension indicate that ponesimod 20 mg o.d. compared to 10 mg o.d. has better clinical and MRI outcomes with similar safety profile.
[i] Olsson T, et al. J Neurol Neurosurg Psychiatry. 2014;85(11):1198-208.
Disclosure: Eva Havrdova has received honoraria/research support from Biogen, Sanofi Genzyme, Merck Serono, Novartis, Roche and Teva; and participated on advisory boards for Actelion, Biogen, Sanofi Genzyme, Merck Serono, Novartis, Celgene.
Anat Achiron has received consulting fees from EMD Serono, Genzyme, and Roche; and has conducted contracted research for Bayer, Biogen Idec, EMD Serono, Genzyme, and Roche.
Patricia Coyle has received consulting fees from Accordant, Acorda, Bayer, Biogen, Celgene, Genentech/Roche, Genzyme/Sanofi, Novartis, Serono, and Teva; and research funding from Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, and Novartis.
Daniele D´Ambrosio is an employee of Actelion Pharmaceuticals Ltd.
Juha-Pekka Erälinna has participated on advisory councils and received travel grants and consultancy honoraria from Biogen, Genzyme, Merck, Novartis, Roche and Teva.
Brian Hennessy is an employee of Actelion Pharmaceuticals Ltd.
Ewa Lindenstroem is an employee of Actelion Pharmaceuticals Ltd.
Jan Lycke has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; and has received unconditional research grants from Biogen, Novartis and Teva.
Guillermo Izquierdo received speaker and/or advisory board honoraria from Bayer, Biogen-Idec, Novartis, Sanofi, Merck, Almirall, Roche and Teva, and research funding from Bayer, Biogen-Idec, Novartis, Sanofi, Merck S, Almirall and Teva.
Carlo Pozzilli has served on advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi, Teva, and has received consulting and/or speaker fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi and Teva.
Mark Freedman has received research funding from Genzyme, honoraria or consultation fees from Actelion, BayerHealthcare, BiogenIdec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, and Teva Canada Innovation, and has served on advisory boards or similar groups for Actelion, BayerHealthcare, BiogenIdec, Hoffman La-Roche, Merck Serono, MedDay, Novartis, Sanofi-Aventis. Dr Freedman also participates on a sponsored speaker's bureau for Genzyme.
Abstract: P1151
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Once daily (o.d.) oral treatment with ponesimod 10, 20 or 40 mg, a novel selective S1P1 receptor modulator, significantly reduced the number of new T1 gadolinium-enhancing (Gd+) lesions and showed clinical benefits in a phase II placebo-controlled trial in relapsing-remitting multiple sclerosis (RRMS)[i]. Patients in the ongoing extension of this trial are currently receiving 10 or 20 mg of ponesimod o.d. Objectives: To compare efficacy and safety of ponesimod 20 mg (P20) vs. 10 mg (P10). Methods: Interim analysis of pooled data from patients randomized to ponesimod 10 or 20 mg (but not 40 mg) in the phase II trial or its extension: cut-off date 1 September 2016. Efficacy outcomes included 6-month confirmed disability accumulation (6 m-CDA), annualized relapse rate (ARR), mean number of T1 Gd+ lesions, and new/enlarging T2 lesions. Safety outcomes included frequency of all adverse events (AEs), serious AEs, and AEs leading to trial treatment discontinuation. A negative binomial model was used to analyse ARR and MRI lesion endpoints, and a Cox's proportional hazards model for 6 m-CDA. Results: Cumulative exposures to P10 and P20 were 613.8 and 615.9 years, respectively. At 6 years, the Kaplan-Meier risks of 6 m-CDA were 29.6% and 16.4% for P10 and P20, respectively, corresponding to a 49% (95% confidence interval [CI]: 8-72%; p=0.024) relative reduction (RR) in the P20 arm compared to the P10 arm. The ARR for confirmed relapses was 0.227 and 0.153 with P10 and P20, respectively (RR for P20 arm: 32.5% [95% CI: -3.6-56.1%; p=0.07]). For all relapses (i.e., confirmed and unconfirmed), the RR in the P20 arm was 33.5% (95% CI: 1.2-55.3%; p=0.043). The mean number of T1 Gd+ lesions per subject per scan was 1.371 and 0.768 with P10 and P20 mg, respectively (RR in the P20 arm: 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 with P10 and P20, respectively (RR in the P20 arm: 66.9% [95% CI: 50.3-77.9%; p< 0.0001]). The proportions (%) of P10 and P20 patients with all AEs, serious AEs, and AEs leading to treatment discontinuation were 94.2 vs. 91.0, 15.1 vs.13.8, and 12.2 vs.10.3, respectively. Conclusion: The pooled data from the phase II trial and its ongoing extension indicate that ponesimod 20 mg o.d. compared to 10 mg o.d. has better clinical and MRI outcomes with similar safety profile.
[i] Olsson T, et al. J Neurol Neurosurg Psychiatry. 2014;85(11):1198-208.
Disclosure: Eva Havrdova has received honoraria/research support from Biogen, Sanofi Genzyme, Merck Serono, Novartis, Roche and Teva; and participated on advisory boards for Actelion, Biogen, Sanofi Genzyme, Merck Serono, Novartis, Celgene.
Anat Achiron has received consulting fees from EMD Serono, Genzyme, and Roche; and has conducted contracted research for Bayer, Biogen Idec, EMD Serono, Genzyme, and Roche.
Patricia Coyle has received consulting fees from Accordant, Acorda, Bayer, Biogen, Celgene, Genentech/Roche, Genzyme/Sanofi, Novartis, Serono, and Teva; and research funding from Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, and Novartis.
Daniele D´Ambrosio is an employee of Actelion Pharmaceuticals Ltd.
Juha-Pekka Erälinna has participated on advisory councils and received travel grants and consultancy honoraria from Biogen, Genzyme, Merck, Novartis, Roche and Teva.
Brian Hennessy is an employee of Actelion Pharmaceuticals Ltd.
Ewa Lindenstroem is an employee of Actelion Pharmaceuticals Ltd.
Jan Lycke has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; and has received unconditional research grants from Biogen, Novartis and Teva.
Guillermo Izquierdo received speaker and/or advisory board honoraria from Bayer, Biogen-Idec, Novartis, Sanofi, Merck, Almirall, Roche and Teva, and research funding from Bayer, Biogen-Idec, Novartis, Sanofi, Merck S, Almirall and Teva.
Carlo Pozzilli has served on advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi, Teva, and has received consulting and/or speaker fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi and Teva.
Mark Freedman has received research funding from Genzyme, honoraria or consultation fees from Actelion, BayerHealthcare, BiogenIdec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, and Teva Canada Innovation, and has served on advisory boards or similar groups for Actelion, BayerHealthcare, BiogenIdec, Hoffman La-Roche, Merck Serono, MedDay, Novartis, Sanofi-Aventis. Dr Freedman also participates on a sponsored speaker's bureau for Genzyme.