Contributions
Abstract: 129
Type: Oral
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: The EXPAND study demonstrated that siponimod, a selective modulator of sphingosine 1-phosphate receptor subtypes 1 and 5, significantly delayed confirmed disability progression in patients with secondary progressive multiple sclerosis (SPMS).
Objective: To evaluate the effect of siponimod versus placebo on predefined magnetic resonance imaging (MRI) outcomes in patients with SPMS.
Methods: Patients were randomised 2:1 to receive siponimod or placebo. MRI scans were performed at baseline and every 12 months thereafter and were analysed by a central reading centre. Key MRI outcomes included: T2 lesion volume (T2LV), number of new or enlarging T2 lesions, number of gadolinium-enhancing (Gd+) lesions, and brain volume loss assessed by percent brain volume change (PBVC). The full analysis set (FAS) comprises of patients who received ≥1 dose of study drug as per original randomisation. The per-protocol analysis set (PPS) consists of all FAS patients without major protocol deviations and includes efficacy data only up to discontinuation of double-blinded treatment.
Results: Treatment benefits in favour of siponimod were observed for all key outcomes and the analysis sets investigated. Post-baseline MRI data was available from >80% of the 1651 randomised patients (siponimod 2mg N=1099; placebo N=546). The adjusted mean differences in the change from baseline vs placebo were (FAS/PPS): for T2LV (mm3) at M12, −613/−634; M24, −778/−830 (p< 0.0001 for all), and for PBVC at M12, 0.175/0.221 (p< 0.0001 for both); M24, 0.128/0.277 (p=0.0196/p< 0.0001). Siponimod reduced the average T1 Gd+ lesion count over M12 and 24 by 86.6% and 91.1% and the average count of new or enlarging T2 lesions by 80.6% and 85.3% in the FAS and PPS, respectively (p< 0.0001 for all).
Conclusion: Siponimod significantly reduced MRI activity and slowed brain volume loss in patients with SPMS already at M12 with effects sustained at M24. These results, together with the clinically observed reduction in confirmed disability progression reported previously, corroborate the positive impact of treatment with siponimod in patients with SPMS.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Robert Fox has received compensation for serving as consultant or speaker for Allozyne, Avanir, Biogen Idec, Novartis, Questcor, and Teva Pharmaceutical Industries. He or the institution he works for has received research support from Novartis. Douglas L. Arnold has served on advisory boards, received speaker honoraria, or served as a consultant, for Acorda, Biogen, F. Hoffmann-La Roche Ltd, Medday, MedImmune, Mitsubishi, Novartis, Receptos/Celgene, and Sanofi-Aventis; has received grants from Biogen and Novartis; and has an equity interest in NeuroRx Research. Amit Bar-Or has received personal compensation for consulting, serving on scientific advisory boards, and/or speaking activities from Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly, F. Hoffmann-La Roche Ltd., Genentech, GlaxoSmithKline (GSK), Guthy-Jackson/GGF, Merck Serono, Novartis, Ono Pharmacia, Sanofi-Aventis, Teva Neuroscience, and Wyeth. Bruce Cree has received personal compensation for consulting from Abbvie, Biogen Idec, EMD Serono and Novartis. Gavin Giovannoni is a steering committee member on the daclizumab trials for AbbVie; is a steering committee member on the BG12 and daclizumab trials for Biogen-Idec; and has received consultancy fees for advisory board meetings, honoraria for speaking at the physicians' summit, and consultancy fees for advisory board meetings and steering committee for oral cladribine trials for Merck-Serono; is a steering committee member on fingolimod and siponimod trials for Novartis, is a steering committee member on the laquinimod trials for Teva, has received consultancy fees for advisory board meetings from Genzyme-Sanofi, has received honoraria for speaking at several medical education meetings, is a steering committee member on ocrelizumab trials for Roche, and has received consultancy fees in relation to DSMB activities for Synthon BV and Co-chief editor of Multiple Sclerosis and Related Disorders (Elsevier).
Ralf Gold has received compensation for serving as consultant or speaker from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience, and he or the institution he works for has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. He has received honoraria as Journal Editor from SAGE and Thieme Verlag.
Patrick Vermersch has received honoraria and consulting fees from Biogen Idec, Genzyme-Sanofi, Bayer, Novartis, Merck Serono, GSK, Servier and Almirall and received research support from Biogen Idec, Genzyme-Sanofi, Bayer, and Merck Serono.
Harald Pohlmann is an employee of Novartis Pharma AG, Basel, Switzerland.
Tatiana Sidorenko is an employee of Novartis Pharma AG, Basel, Switzerland.
Christian Wolf is a partner at Lycalis sprl. He is serving as a consultant to Novartis and has also received compensation for serving as a consultant for to-BBB, Desitin, Investitionsbank Berlin, Keyrus, Synthon, Mylan, ICON, and Teva.
Davorka Tomic is an employee of Novartis Pharma AG, Basel, Switzerland.
Frank Dahlke is an employee of Novartis Pharma AG, Basel, Switzerland.
Ludwig Kappos has received no personal compensation. LK's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
Abstract: 129
Type: Oral
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: The EXPAND study demonstrated that siponimod, a selective modulator of sphingosine 1-phosphate receptor subtypes 1 and 5, significantly delayed confirmed disability progression in patients with secondary progressive multiple sclerosis (SPMS).
Objective: To evaluate the effect of siponimod versus placebo on predefined magnetic resonance imaging (MRI) outcomes in patients with SPMS.
Methods: Patients were randomised 2:1 to receive siponimod or placebo. MRI scans were performed at baseline and every 12 months thereafter and were analysed by a central reading centre. Key MRI outcomes included: T2 lesion volume (T2LV), number of new or enlarging T2 lesions, number of gadolinium-enhancing (Gd+) lesions, and brain volume loss assessed by percent brain volume change (PBVC). The full analysis set (FAS) comprises of patients who received ≥1 dose of study drug as per original randomisation. The per-protocol analysis set (PPS) consists of all FAS patients without major protocol deviations and includes efficacy data only up to discontinuation of double-blinded treatment.
Results: Treatment benefits in favour of siponimod were observed for all key outcomes and the analysis sets investigated. Post-baseline MRI data was available from >80% of the 1651 randomised patients (siponimod 2mg N=1099; placebo N=546). The adjusted mean differences in the change from baseline vs placebo were (FAS/PPS): for T2LV (mm3) at M12, −613/−634; M24, −778/−830 (p< 0.0001 for all), and for PBVC at M12, 0.175/0.221 (p< 0.0001 for both); M24, 0.128/0.277 (p=0.0196/p< 0.0001). Siponimod reduced the average T1 Gd+ lesion count over M12 and 24 by 86.6% and 91.1% and the average count of new or enlarging T2 lesions by 80.6% and 85.3% in the FAS and PPS, respectively (p< 0.0001 for all).
Conclusion: Siponimod significantly reduced MRI activity and slowed brain volume loss in patients with SPMS already at M12 with effects sustained at M24. These results, together with the clinically observed reduction in confirmed disability progression reported previously, corroborate the positive impact of treatment with siponimod in patients with SPMS.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Robert Fox has received compensation for serving as consultant or speaker for Allozyne, Avanir, Biogen Idec, Novartis, Questcor, and Teva Pharmaceutical Industries. He or the institution he works for has received research support from Novartis. Douglas L. Arnold has served on advisory boards, received speaker honoraria, or served as a consultant, for Acorda, Biogen, F. Hoffmann-La Roche Ltd, Medday, MedImmune, Mitsubishi, Novartis, Receptos/Celgene, and Sanofi-Aventis; has received grants from Biogen and Novartis; and has an equity interest in NeuroRx Research. Amit Bar-Or has received personal compensation for consulting, serving on scientific advisory boards, and/or speaking activities from Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly, F. Hoffmann-La Roche Ltd., Genentech, GlaxoSmithKline (GSK), Guthy-Jackson/GGF, Merck Serono, Novartis, Ono Pharmacia, Sanofi-Aventis, Teva Neuroscience, and Wyeth. Bruce Cree has received personal compensation for consulting from Abbvie, Biogen Idec, EMD Serono and Novartis. Gavin Giovannoni is a steering committee member on the daclizumab trials for AbbVie; is a steering committee member on the BG12 and daclizumab trials for Biogen-Idec; and has received consultancy fees for advisory board meetings, honoraria for speaking at the physicians' summit, and consultancy fees for advisory board meetings and steering committee for oral cladribine trials for Merck-Serono; is a steering committee member on fingolimod and siponimod trials for Novartis, is a steering committee member on the laquinimod trials for Teva, has received consultancy fees for advisory board meetings from Genzyme-Sanofi, has received honoraria for speaking at several medical education meetings, is a steering committee member on ocrelizumab trials for Roche, and has received consultancy fees in relation to DSMB activities for Synthon BV and Co-chief editor of Multiple Sclerosis and Related Disorders (Elsevier).
Ralf Gold has received compensation for serving as consultant or speaker from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience, and he or the institution he works for has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. He has received honoraria as Journal Editor from SAGE and Thieme Verlag.
Patrick Vermersch has received honoraria and consulting fees from Biogen Idec, Genzyme-Sanofi, Bayer, Novartis, Merck Serono, GSK, Servier and Almirall and received research support from Biogen Idec, Genzyme-Sanofi, Bayer, and Merck Serono.
Harald Pohlmann is an employee of Novartis Pharma AG, Basel, Switzerland.
Tatiana Sidorenko is an employee of Novartis Pharma AG, Basel, Switzerland.
Christian Wolf is a partner at Lycalis sprl. He is serving as a consultant to Novartis and has also received compensation for serving as a consultant for to-BBB, Desitin, Investitionsbank Berlin, Keyrus, Synthon, Mylan, ICON, and Teva.
Davorka Tomic is an employee of Novartis Pharma AG, Basel, Switzerland.
Frank Dahlke is an employee of Novartis Pharma AG, Basel, Switzerland.
Ludwig Kappos has received no personal compensation. LK's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.