Data from the open-label extension of the EXPAND study of patients with secondary progressive multiple sclerosis (SPMS) showed that early treatment benefits with siponimod (Mayzent), a selective sphingosine 1-phosphate (S1P) receptor modulator, were preserved through the end of the study.
This analysis was presented as part the American Academy of Neurology (AAN) 2020 Science Highlights, which featured research online from the AAN annual meeting, which had been cancelled because of the Covid-19 pandemic. This analysis compared SPMS patients treated with siponimod during both the core (through 2 years) and extension (up to 5 years) periods of the EXPAND trial versus patients treated with placebo during the core who were then switched to siponimod in the extension period.
The continuous treatment group had lower risks of confirmed disability progression and cognitive decline than the switch group, reported Ludwig Kappos, MD, of the University of Basel in Switzerland, and co-authors. Specifically:
- The risk of 6-month confirmed disability progression on the Expanded Disability Status Scale (EDSS) was reduced by 22.3% (HR 0.78; 95% CI 0.66-0.92; P = 0.0026) in the continuous siponimod group.
- The risk of worsening on the Symbol Digit Modalities Test (SDMT; a cognition performance outcome measure in MS) was reduced by 23% (HR 0.77; 95% CI 0.65-0.92; P = 0.0047) in the continuous siponimod group.
- Overall annualized relapse rate (ARR) was significantly lower in the continuous group versus switch group; between-group comparison showed a 52% reduction (rate ratio 0.48; 95% CI 0.37-0.62; P < 0.0001).
“The core EXPAND study provided evidence for significant and clinically important effect of siponimod regarding disability progression,” Kappos said. “The mean observation time on the core study was somewhat more than 1.5 years; therefore, longer-term data are necessary to assess both the sustained ability of the effect and the longer-term adverse event profile.”
The EXPAND study, a placebo-controlled, randomized phase III trial, showed siponimod 2 mg/day reduced confirmed EDSS score disability progression over ≤36 months in patients with SPMS. In the EXPAND core study, siponimod reduced the relative risk of 3-month confirmed disability progression by 21% and 6-month confirmed disability progression by 26% compared with placebo and showed benefits in cognitive processing speed. Based on EXPAND data, the FDA approved siponimod in 2019 for clinically isolated syndrome, relapsing remitting MS, and secondary progressive disease.
To assess longer-term efficacy and safety of siponimod in patients with SPMS from the core and extension parts of the EXPAND study, researchers included EXPAND participants who received at least one dose of randomized treatment (siponimod 2 mg versus placebo) through the 36-month extension data cutoff of April 2019.
Efficacy analyses compared continuous and switch group participants on measures on 6-month confirmed disability progression on the EDSS, cognitive worsening by 4 points or more on the SDMT, and annualized relapse rate.
A total of 1,224 (74.1% of 1,651 randomized) patients entered the extension study. By the April 2019 cutoff, 92.2% of the participants had been exposed to siponimod for 6 or more months. As of April 2019, the mean exposure to siponimod for extension participants was 39.4 months (42.6 months in the continuous group; 31.0 months in the switch group), corresponding to 4,981.7 patient-years. In the continuous siponimod group, 25.3% had 5 or more years of observation.
The analysis showed that time to 6-month confirmed disability progression was prolonged by 49% in the continuous group. Time to 6-month cognitive worsening on the SDMT was prolonged by 55%.
The results indicate the benefit of early intervention in patients with active secondary progressive MS, noted Barry Hendin, MD, of Banner-University Medical Center Phoenix in Arizona, who was not involved with the study.
“Patients who received 5 years of continuous therapy with siponimod showed significantly less progression in physical and cognitive disability, measured by symbol digit modality testing, compared to patients who initially received placebo and were switched to active therapy after 2 years,” he pointed out.
Incidence rates of adverse events per 100 patient-years during the extension period were consistent with the controlled treatment period and no new safety findings were seen, the researchers reported. Serious adverse events included basal cell carcinoma, urinary tract infection, and seizure.
The findings show the importance of early treatment intervention for MS patients experiencing progression, study author Bruce Cree, MD, PhD, of University of California, San Francisco, noted. “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,” he said.
Data from the open-label extension of the EXPAND study of patients with secondary progressive multiple sclerosis (SPMS) showed early treatment benefits with siponimod (Mayzent) were preserved through the end of the study.
Findings are based on analyses prepared for the American Academy of Neurology annual meeting and have not yet been peer-reviewed.
Paul Smyth, MD, Contributing Writer, BreakingMED™
The study was funded by Novartis.
Kappos has received research support from Bayer, Biogen, Innosuisse, Novartis, the Swiss MS Society, the Swiss National Research Foundation, and the European Union. Cree has received personal compensation from Akili, Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.
Hendin consults for Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Bristol-Myers Squibb.
Cat ID: 131
Topic ID: 82,131,730,131,36,192,167