Efficacy of Siponimod in secondary progressive multiple sclerosis patients with active disease: the EXPAND study subgroup analysis
ECTRIMS Online Library. Gold R. 09/12/19; 279110; P750
Ralf Gold
Ralf Gold
Contributions
Abstract

Abstract: P750

Type: Poster Sessions

Abstract Category: Clinical aspects of MS - Progressive MS

R. Gold1, L. Kappos2, A. Bar-Or3, P. Vermersch4, G. Giovannoni5, R. Fox6, N. Rouyrre7, G. Karlsson7, B.A.C. Cree8

1Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany, 2Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland, 3Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada, 4Department of Neurology, University of Lille, Lille, France, 5Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 6Mellen Center for Treatment and Research in Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States, 7Novartis Pharma AG, Basel, Switzerland, 8UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, United States

Background: Siponimod, a selective sphingosine 1-phosphate receptor (S1P1,5) modulator, demonstrated clinically relevant effects in a typical secondary progressive multiple sclerosis (SPMS) population in the Phase 3 EXPAND study, with 21% and 26% reductions in 3- and 6-month confirmed disability progression (CDP). Siponimod was recently approved in the US for the treatment of relapsing forms of multiple sclerosis (MS), including active SPMS.
Objective: To assess the efficacy of siponimod versus placebo in a subgroup of active SPMS patients.
Methods: Post hoc subgroup analysis was performed in patients with active disease (defined as the presence of relapses in the 2 years before screening and/or ≥1 T1 gadolinium-enhancing [Gd+] lesion at baseline), treated with siponimod 2 mg or placebo in the EXPAND study. Efficacy outcomes were time to 3-month CDP and 6-month CDP as per Expanded Disability Status Scale (EDSS), time to 6-month confirmed 4-point change of cognitive processing speed on the Symbol Digit Modalities Test (SDMT); annualised relapse rate (ARR); and MRI outcomes (number of T1 Gd+ and T2 lesions, change from baseline in T2 lesion volume [T2LV], percent brain volume change [PBVC]).
Results: This analysis included 779 SPMS patients with active disease (siponimod [n=516], placebo [n=263]); mean (SD) duration since MS onset was 15.6 (7.99) years, mean (SD) baseline EDSS score was 5.4 (1.05). The proportion of patients with MS relapse in the 2 years prior to the study was 76% and with Gd+ lesions at baseline 45%. Siponimod significantly reduced 3-month CDP risk by 31% (HR [95% CI]: 0.69 [0.53, 0.91]; p=0.0094) and 6-month CDP risk by 37% (HR [95% CI]: 0.63 [0.47, 0.86], p=0.0040) versus placebo. The risk of 6-month confirmed 4-point SDMT worsening was reduced by 27% (HR [95% CI]: 0.73 [0.53, 1.01], p=0.0561); ARR was reduced by 46% (p=0.0005), T1 Gd+ lesion number by 85% (p< 0.0001), and new/enlarging T2 lesion number by 80% (p< 0.0001) versus placebo. The adjusted mean difference over Months 12 and 24 (siponimod versus placebo) in T2LV was -1161.5 mm3 (p< 0.0001), and 0.128 (p=0.1153) for PBVC.
Conclusions: In the main analysis, siponimod was effective in reducing disability progression across the SPMS spectrum. In this subgroup of active SPMS patients, benefits on disability progression were more pronounced with clinically relevant effects across disability progression, cognitive processing speed, and MRI inflammatory disease activity.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Ralf Gold has received compensation for serving as a consultant or speaker from Bayer HealthCare, Biogen, Merck, Novartis and Teva. He or the institution he works for has received research support from Bayer HealthCare, Biogen, Merck, Novartis and Teva; he has also received honoraria as a Journal Editor from SAGE and Thieme Verlag.
Bruce A.C. Cree has received personal compensation for consulting from Abbvie, Akili, Alexion, Biogen, EMD Serono, Novartis, Sanofi Genzyme and TG Therapeutics.
Patrick Vermersch has received honoraria and consulting fees from Biogen, Sanofi, Teva, Novartis, Merck and Almirall, and research support from Biogen, Sanofi, Bayer, and Merck.
Gavin Giovannoni is a steering committee member on the daclizumab trials for AbbVie, the BG12 and daclizumab trials for Biogen Idec, the fingolimod and siponimod trials for Novartis, the laquinimod trials for Teva and the ocrelizumab trials for Roche. He has also received consultancy fees for advisory board meetings for oral cladribine trials for Merck KGaA, Genzyme-Sanofi, and in relation to DSMB activities for Synthon BV, as well as honoraria for speaking at the Physicians' summit and several medical education meetings. He is also the Co-Chief Editor of Multiple Sclerosis and Related Disorders (Elsevier).
Robert Fox has received compensation for serving as a consultant or speaker from Allozyne, Avanir, Biogen, Novartis, Questcor and Teva Pharmaceutical Industries. He or the institution he works for has received research support from Novartis.
Amit Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from: Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, MAPI, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme.
Nicolas Rouyrre and Göril Karlsson are employees of Novartis Pharma AG.
Ludwig Kappos' institution (University Hospital Basel) has received the following exclusively for research support: steering committee, advisory board, and consultancy fees (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 (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi and Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi and Teva); royalties (Neurostatus products); licence fees for Neurostatus products; and grants (Bayer HealthCare, Biogen Idec, European Union, INNO-Swiss, Merck, Novartis, Roche Research Foundation, Swiss MS Society and Swiss National Research Foundation).

Abstract: P750

Type: Poster Sessions

Abstract Category: Clinical aspects of MS - Progressive MS

R. Gold1, L. Kappos2, A. Bar-Or3, P. Vermersch4, G. Giovannoni5, R. Fox6, N. Rouyrre7, G. Karlsson7, B.A.C. Cree8

1Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany, 2Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland, 3Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada, 4Department of Neurology, University of Lille, Lille, France, 5Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 6Mellen Center for Treatment and Research in Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States, 7Novartis Pharma AG, Basel, Switzerland, 8UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, United States

Background: Siponimod, a selective sphingosine 1-phosphate receptor (S1P1,5) modulator, demonstrated clinically relevant effects in a typical secondary progressive multiple sclerosis (SPMS) population in the Phase 3 EXPAND study, with 21% and 26% reductions in 3- and 6-month confirmed disability progression (CDP). Siponimod was recently approved in the US for the treatment of relapsing forms of multiple sclerosis (MS), including active SPMS.
Objective: To assess the efficacy of siponimod versus placebo in a subgroup of active SPMS patients.
Methods: Post hoc subgroup analysis was performed in patients with active disease (defined as the presence of relapses in the 2 years before screening and/or ≥1 T1 gadolinium-enhancing [Gd+] lesion at baseline), treated with siponimod 2 mg or placebo in the EXPAND study. Efficacy outcomes were time to 3-month CDP and 6-month CDP as per Expanded Disability Status Scale (EDSS), time to 6-month confirmed 4-point change of cognitive processing speed on the Symbol Digit Modalities Test (SDMT); annualised relapse rate (ARR); and MRI outcomes (number of T1 Gd+ and T2 lesions, change from baseline in T2 lesion volume [T2LV], percent brain volume change [PBVC]).
Results: This analysis included 779 SPMS patients with active disease (siponimod [n=516], placebo [n=263]); mean (SD) duration since MS onset was 15.6 (7.99) years, mean (SD) baseline EDSS score was 5.4 (1.05). The proportion of patients with MS relapse in the 2 years prior to the study was 76% and with Gd+ lesions at baseline 45%. Siponimod significantly reduced 3-month CDP risk by 31% (HR [95% CI]: 0.69 [0.53, 0.91]; p=0.0094) and 6-month CDP risk by 37% (HR [95% CI]: 0.63 [0.47, 0.86], p=0.0040) versus placebo. The risk of 6-month confirmed 4-point SDMT worsening was reduced by 27% (HR [95% CI]: 0.73 [0.53, 1.01], p=0.0561); ARR was reduced by 46% (p=0.0005), T1 Gd+ lesion number by 85% (p< 0.0001), and new/enlarging T2 lesion number by 80% (p< 0.0001) versus placebo. The adjusted mean difference over Months 12 and 24 (siponimod versus placebo) in T2LV was -1161.5 mm3 (p< 0.0001), and 0.128 (p=0.1153) for PBVC.
Conclusions: In the main analysis, siponimod was effective in reducing disability progression across the SPMS spectrum. In this subgroup of active SPMS patients, benefits on disability progression were more pronounced with clinically relevant effects across disability progression, cognitive processing speed, and MRI inflammatory disease activity.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Ralf Gold has received compensation for serving as a consultant or speaker from Bayer HealthCare, Biogen, Merck, Novartis and Teva. He or the institution he works for has received research support from Bayer HealthCare, Biogen, Merck, Novartis and Teva; he has also received honoraria as a Journal Editor from SAGE and Thieme Verlag.
Bruce A.C. Cree has received personal compensation for consulting from Abbvie, Akili, Alexion, Biogen, EMD Serono, Novartis, Sanofi Genzyme and TG Therapeutics.
Patrick Vermersch has received honoraria and consulting fees from Biogen, Sanofi, Teva, Novartis, Merck and Almirall, and research support from Biogen, Sanofi, Bayer, and Merck.
Gavin Giovannoni is a steering committee member on the daclizumab trials for AbbVie, the BG12 and daclizumab trials for Biogen Idec, the fingolimod and siponimod trials for Novartis, the laquinimod trials for Teva and the ocrelizumab trials for Roche. He has also received consultancy fees for advisory board meetings for oral cladribine trials for Merck KGaA, Genzyme-Sanofi, and in relation to DSMB activities for Synthon BV, as well as honoraria for speaking at the Physicians' summit and several medical education meetings. He is also the Co-Chief Editor of Multiple Sclerosis and Related Disorders (Elsevier).
Robert Fox has received compensation for serving as a consultant or speaker from Allozyne, Avanir, Biogen, Novartis, Questcor and Teva Pharmaceutical Industries. He or the institution he works for has received research support from Novartis.
Amit Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from: Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, MAPI, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme.
Nicolas Rouyrre and Göril Karlsson are employees of Novartis Pharma AG.
Ludwig Kappos' institution (University Hospital Basel) has received the following exclusively for research support: steering committee, advisory board, and consultancy fees (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 (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi and Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi and Teva); royalties (Neurostatus products); licence fees for Neurostatus products; and grants (Bayer HealthCare, Biogen Idec, European Union, INNO-Swiss, Merck, Novartis, Roche Research Foundation, Swiss MS Society and Swiss National Research Foundation).

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies