Save
Efficacy and safety of siponimod in secondary progressive multiple sclerosis - Results of the placebo controlled, double-blind, Phase III EXPAND study
Author(s): ,
L Kappos
Affiliations:
Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, Basel, Switzerland
,
A Bar-Or
Affiliations:
Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
,
B Cree
Affiliations:
Multiple Sclerosis Centre, University of California San Francisco, San Francisco, CA
,
R Fox
Affiliations:
Mellen Centre for Treatment and Research in Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States
,
G Giovannoni
Affiliations:
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
,
R Gold
Affiliations:
Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany
,
P Vermersch
Affiliations:
University of Lille, Department of Neurology, Lille City, France
,
S Arnould
Affiliations:
Novartis Pharma AG, Basel, Switzerland
,
T Sidorenko
Affiliations:
Novartis Pharma AG, Basel, Switzerland
,
C Wolf
Affiliations:
Lycalis sprl, Brussels, Belgium
,
E Wallstroem
Affiliations:
Novartis Pharma AG, Basel, Switzerland
F Dahlke
Affiliations:
Novartis Pharma AG, Basel, Switzerland
ECTRIMS Online Library. Kappos L.
Sep 16, 2016; 147077
Ludwig Kappos
Ludwig Kappos
Login now to access Regular content available to all registered users.

You may also access this content "anytime, anywhere" with the Free MULTILEARNING App for iOS and Android
Abstract
Discussion Forum (0)
Rate & Comment (0)

Abstract: 250

Type: LB Oral

Abstract Category: Late Breaking News

Background: There is high unmet need for treatments that delay disability progression in secondary progressive multiple sclerosis (SPMS). Siponimod (BAF312) is an orally active selective modulator of the sphingosine-1-phosphate receptor subtypes 1 and 5. EXPAND is the largest randomised controlled study in SPMS to date.

Objective: EXPAND is a phase 3, multicentre, randomised, double-blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of siponimod in treatment of SPMS.

Design/methods: Patients with SPMS, defined by a progressive increase in disability (of ≥6 months duration) in the absence or independent of relapses, aged 18‒60 years and an Expanded Disability Status Scale (EDSS) score from 3.0‒6.5 were enrolled. Eligible patients were randomised (2:1) to receive either 2mg once daily siponimod (following initial dose titration starting at 0.25mg) or matching placebo. The event-driven study design allowed the blinded Core study stop after a pre-specified number of confirmed disability progression (CDP) events occurred. The primary efficacy outcome was time to 3-month CDP measured by EDSS. The key secondary outcomes were time to confirmed worsening of ≥20% from baseline in the timed 25-foot walk test and T2 lesion volume change from baseline. Safety assessments included reporting of adverse events (AEs), serious AEs (SAEs) and clinically notable laboratory abnormalities. Patients who completed the Core phase were offered to receive open-label siponimod in the Extension phase.

Results: Overall, 1651 patients were randomised in 31 countries. Baseline demographics and disease characteristics were previously reported, and they are representative of a patient population with SPMS. Overall, 1363 (83%) patients completed the Core study. Median time on study at core study completion was 21 months with majority of patients (87%) participating for ≥1 year. There were 449 CDP events (each patient could maximally contribute one event for the primary endpoint). AEs were reported in 85.3% and SAEs in 16.7% of patients.

Conclusions: Top line efficacy and safety results of the EXPAND study will be presented. The results of this large controlled study that recruited an active SPMS population with and without superimposed relapses will determine if siponimod delays disability progression in SPMS, and will contribute to a better understanding of the natural history of SPMS in a well-controlled trial setting.

Disclosure: Funding source: This study is supported by Novartis Pharma AG, Basel, Switzerland.

Ludwig Kappos" 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; royalties from Neurostatus Systems GmbH and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.

Amit Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees from Amplimmune, Biogen Idec, Diogenix, Genentech, Sanofi-Genzyme, GlaxoSmithKline, Novartis, Ono Pharma, Teva Neuroscience, Receptos Inc., Roche, and Merck/EMD Serono and has received grant support from Amplimmune, Biogen Idec, Diogenix, Genentech, Sanofi- Genzyme, GlaxoSmithKline, Novartis, Ono Pharma, Teva Neuroscience, Receptos Inc., Roche, and Merck/EMD Serono.

Bruce Cree has received personal compensation for consulting from Abbvie, Biogen Idec, EMD Serono, MedImmune, Novartis, Genzyme/Sanofi Aventis, and Teva Neurosciences; contracted research support (including clinical trials) from Acorda, Biogen Idec, EMD Serono, Hoffman La Roche, MedImmune, and Teva Neurosciences.

Robert Fox has received compensation for serving as consultant or speaker from Allozyne, Avanir, Biogen Idec, Novartis, Questcor, and Teva Pharmaceutical Industries; he or the institution he works for has received research support from Novartis.

Gavin Giovannoni is steering committee member on the Daclizumab trials for AbbVie, steering committee member on the BG12 and Daclizumab trials for Biogen-Idec, has received consultancy fees for advisory board meetings, honoraria for speaking at Physicians summit, consultancy fees for advisory board meetings and steering committee for oral cladribine trials for Merck-Serono, steering committee member on Fingolimod and Siponimod trials for Novartis, steering committee member on the laquinimod trials for Teva, consultancy fees for advisory board meetings for Genzyme-Sanofi, honoraria for speaking at several medical education meetings, steering committee member on Ocrelizumab trials for Roche, 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.

Patrick Vermersch has received honoraria and consulting fees from Biogen Idec, Genzyme-Sanofi, Bayer, Novartis, Merck Serono, GSK and Almirall; research support from Biogen Idec, Genzyme-Sanofi, Bayer, and Merck Serono.

Sophie Arnould, Tatiana Sidorenko, Erik Wallstroem and Frank Dahlke are employees of Novartis.

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 and Teva.

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings