The Novartis agent showed benefit in patients who had multiple sclerosis both with and without relapses.
Bruce Cree, MD, PhD, MAS
Data from the phase 3 EXPAND clinical trial (NCT01665144) of siponimod (Mayzent; Novartis) demonstrated the treatment’s ability to reduce the risk of confirmed disability progression (CDP) in patients with secondary progressive multiple sclerosis (SPMS) with or without relapses.
The risk reductions in non-relapsing patients in the 1 and 2 years before the study were 18% (hazard ratio [HR], 0.82; 95% CI, 0.66—1.02) and 13% (HR, 0.87; 95% CI, 0.68–1.11), respectively. For 3-and 6-month CDP, the risk reductions were 25% (HR, 0.75; 95% CI, 0.59–0.96) and 18% (HR, 0.82; 95% CI, 0.62–1.08), respectively.
Data presented at the 2020 Consortium of Multiple Sclerosis Centers (CMSC) Virtual Annual Meeting, May 26-29, 2020 revealed risk reductions of 33% and 33% for 3-month CDP in years 1 and 2, and 30% and 37% for 6-month CDP in years 1 and 2, respectively, in relapsing patients.
Bruce Cree, MD, PhD, MAS, lead author, and neurologist, UCSF Multiple Sclerosis Center, and colleagues found that siponimod reduced 3-month CDP by 14% to 20% and 6-month CDP by 29% to 33% in non-relapsing patients across the Month 12, Month 18, and Month 24 timepoints.
Cox model censoring at relapse confirmed these beneficial effects, reaching nominal statistical significance for 6-month CDP (HR, 0.77; 95% CI, 0.62—0.96).
The goal of the EXPAND trial was to assess the impact of siponimod on CDP in patients with and without relapses to uncouple treatment effects of CDP from those on relapses. EXPAND contained patients aged 18 to 60 years with SPMS and EDSS scores ranging from 3.0 to 6.5, and administered once-daily oral siponimod 2 mg or placebo for up to 3 years.
Previously reported results from the trial showed that siponimod reduced the risk of 3- and 6-month CDP by 21% and 26%, respectively, compared with placebo, in patients with SPMS. Additionally, a subgroup analysis of EXPAND suggested that a proportion of the effect of siponimod on CDP was attributable to effects on relapse-independent disability progression. The therapy’s 3-month CDP reductions in EXPAND helped lend support to its FDA approval in March 2019. It became the first drug approved for patients with SPMS in more than a decade.2
Findings from EXPAND also suggested that patients with SPMS who are treated with siponimod experience a sustained benefit, with a slowing of physical disability progression and additional cognitive protection. Of the 1099 who were administered the sphinogosine 1-phosphate (S1P) receptor modulator and 546 given placebo, significant treatment effects were detected over the 36-month period for Expanded Disability Status Scale (EDSS) scores (P =.20), as well as both the Motor Integration (MI; P = .014) and Collateral (C; P = .021) subscales.3
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1. Cree BAC, Fox RJ, Giovannoni G, et al. Siponimod affects disability progression in patients with secondary progressive multiple sclerosis independent of relapse activity: Results from the phase 3 EXPAND study. Int J MS Care. 2020;22(2 Suppl). DXT10.
2. Novartis receives FDA approval for Mayzent® (siponimod), the first oral drug to treat secondary progressive MS with active disease [press release]. Basel, Switzerland: Novartis; Published March 26, 2019. novartis.gcs-web.com/Novartis-receives-FDA-approval-for-Mayzent-siponimod-the-first-oral-drug-to-treat-secondary-progressive-MS-with-active-disease. Accessed March 26, 2019.
3. Cutter G, Meng X, Bar-Or A, et al. Effect of Siponimod on Disability in EXPAND Re-examined with Two New Subscales of the Expanded Disability Status Scale in Patients with SPMS. Neurology. 2020; 94 (15 Supplement): 4051.