Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND...

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Siponimod, a sphingosine 1-phosphate receptor modulator, is approved for active secondary progressive multiple sclerosis (aSPMS).
• Existing data from the EXPAND study primarily included a broader SPMS population.
• Characterizing siponimod's efficacy and safety specifically in the aSPMS subgroup is crucial.

Purpose of the Study:

• To perform a post hoc analysis of the EXPAND study to evaluate siponimod's efficacy and safety in participants with aSPMS.
• To assess the impact of siponimod on disability progression, cognitive function, and MRI outcomes in this specific patient population.

Main Methods:

• A post hoc analysis of 779 participants with aSPMS from the phase 3 EXPAND study.
• Participants received oral siponimod (2 mg/day) or placebo for up to 3 years.
• Outcomes included 3- and 6-month confirmed disability progression (3mCDP/6mCDP), Timed 25-Foot Walk (T25FW), Symbol Digit Modalities Test (SDMT), T2 lesion volume (T2LV), T1 gadolinium-enhancing lesions, and new/enlarging T2 lesions.

Main Results:

• Siponimod significantly reduced the risk of 3mCDP (31%) and 6mCDP (37%) versus placebo (p < 0.01).
• A significant increase in the likelihood of 6-month confirmed SDMT improvement (62%; p = 0.007) and a trend towards reduced SDMT worsening (27%; p = 0.060) were observed.
• Siponimod markedly reduced T2LV increase, T1 Gd+ lesions, and new/enlarging T2 lesions compared to placebo (p < 0.0001).

Conclusions:

• In patients with aSPMS, siponimod demonstrated a significant reduction in the risk of disability progression.
• Siponimod treatment was associated with beneficial effects on cognitive function, as measured by the SDMT.
• The drug also showed significant improvements in key MRI markers of disease activity, supporting its efficacy in aSPMS.