Five-year EXPAND study data suggest that Novartis’s S1P receptor modulator has sustained benefit and delays disability over long-term treatment in patients with SPMS.
Bruce Cree, MD, PhD, MAS, clinical research director, and George A. Zimmermann Endowed Professor in Multiple Sclerosis, UCSF School of Medicine
Bruce Cree, MD, PhD, MAS
A new analysis of data from the EXPAND clinical trial of siponimod (Mayzent; Novartis) in patients with secondary progressive multiple sclerosis (SPMS) suggests that the sphingosine 1-phosphate (S1P) receptor modulator has a sustained benefit and a delay in disability over long-term treatment.1,2
All told, data from the 5-year, open-label extension study showed that those who continued on siponimod treatment (n = 878) were less likely to experience both 3-month confirmed disability progression (CDP; P = .0064) and 6-month CDP (P = .0048) compared to those who switched from placebo (n = 346). As well, incidence rates of adverse events per 100 patient-years in the long-term follow-up were consistent with the controlled treatment period, with no new safety findings observed.
“The data continue to show that Mayzent has the ability to help patients maintain independence for longer through its long-term effect on delaying progression and cognitive impairment,” Norman Putzki, MD, Global Head of Development, Neuroscience, Novartis, said in a statement.3 “Novartis is committed to reimagining medicine for patients with progressive diseases and with Mayzent, Novartis offers patients hope for improved health outcomes.”
The data, collected by Bruce Cree, MD, PhD, MAS, clinical research director, and George A. Zimmermann Endowed Professor in Multiple Sclerosis, UCSF School of Medicine, and colleagues, were accepted to be presented the American Academy of Neurology (AAN) 2020 Annual Meeting.
This analysis of EXPAND included 1124 patients (74% of 1651 randomized patients), all of whom received ≥1 dose of randomized treatment. The efficacy analyses included time-to-3- and 6-month CDP on the Expanded Disability Status Scale (EDSS), time-to-6-month confirmed worsening—defined as ≥4 points on Symbol Digit Modalities Test—and annualized relapse rate (ARR).
“These data highlight the critical importance of early treatment intervention with a disease-modifying treatment, such as Mayzent, to ensure the best possible long-term outcomes for patients with MS who are experiencing progression,” Cree said in a statement. “It’s never too early to stay ahead of progression in multiple sclerosis since the early identification of physical and cognitive changes—even subtle ones—can indicate MS disease progression and therefore allow for timely intervention.”
A reduction in ARR of 52% was observed for the continuing group (0.054) compared to the switch group (0.097; P <.0001).
The median time-to-6-month CDP was not reached for the continuing group, while the placebo-switch group’s median time was 51.7 months. Time to 6-month CDP was prolonged enough to equate to a delay of 54% for the 25th percentile in the continuing group (21.0 months) compared with the placebo switch group (13.6 months).
Additionally, post-hoc analysis from EXPAND suggested that siponimod consistently reduced cortical grey matter and thalamic atrophy in those with SPMS. Across all subgroups, the reduction in cortical grey matter atrophy compared to placebo ranged from 48% to 116% (P <.01 at both 1 year and 2 years), and thalamic atrophy was reduced by 30% to 68% (P <.05 at both 1 year and 2 years). Although, thalamic atrophy was not significantly reduced for those with a disease duration >15 years after 1 year (P = .1029).
The time-to-6-month clinical worsening on the SDMT was delayed in those who continued to the placebo switch group (P = .0014), and the risk of worsening on the SDMT was reduced by 23%, corresponding to a delay of 62% for the 25th percentile (continuing group: 29.6 months; placebo switch group: 18.3 months).
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1. Kappos L, et al. Long-term Efficacy and Safety of Siponimod in Patients with SPMS: EXPAND Extension Analysis up to 5 Years. Neurology. 2020; 94 (15 Supplement): 4128.
2. Fox R, et al. Siponimod Reduces Grey Matter Atrophy in Patients with Secondary Progressive Multiple Sclerosis: Subgroup Analyses from the EXPAND study. Neurology. 2020; 94 (15 Supplement): 4037.
3. Novartis announces new Mayzent® (siponimod) data show sustained effect in delaying disability for up to five years in patients with secondary progressive multiple sclerosis (SPMS) [press release]. Basel, Switzerland: Novartis; Published April 21, 2020. Accessed April 22, 2020. globenewswire.com/news-release/2020/04/21/2019014/0/en/Novartis-announces-new-Mayzent-siponimod-data-show-sustained-effect-in-delaying-disability-for-up-to-five-years-in-patients-with-secondary-progressive-multiple-sclerosis-SPMS.html