Charting Progress: Ozanimod’s Influence on Brain Dynamics in RMS

• ZEPOSIA (ozanimod), a breakthrough approved in March 2020 for Relapsing Forms of Multiple Sclerosis (RMS), utilizes oral sphingosine 1-phosphate (S1P) receptor modulation to impede lymphocyte migration, offering a novel approach in multiple sclerosis treatment.
• ENLIGHTEN (NCT04140305) explores ozanimod’s impact on early RMS. Utilizing advanced imaging techniques, it analyzes whole brain volume (WBV) changes over 1 year, shedding light on potential therapeutic benefits.

At the American Academy of Neurology conference 2024, Bristol Myers Squibb reported the interim findings of the ENLIGHTEN Study. This multicenter, longitudinal, single-arm study explores cognitive processing speed enhancements in RMS patients receiving ozanimod over 3 years. The trial’s completion is anticipated by 2026. This open-label trial explores the impact of ozanimod 0.92 mg in early RMS patients. Percent change in brain volumes over 1 year was analyzed using cutting-edge imaging techniques like SIENA (for WBV), FreeSurfer (for thalamic volume [TV] and medulla oblongata volume [MOV]), a modified hybrid of SIENA and SIENAX methods (mSIENAX-multi time point for cortical grey matter volume [CGMV]), SIENAX (for baseline lateral ventricle volume [LVV]), and VIENA on a 3-dimensional T1-weighted image (for 1-year LVV). Least squares means and 95% confidence intervals were calculated for percentage changes, employing a sophisticated mixed-effects model adjusted for baseline volume and age.

A comprehensive analysis of 185 patients in the ozanimod study revealed promising results. Most participants were female and DMT-naive. Baseline brain volumes were characterized by mean values, with subsequent 1-year changes indicating subtle fluctuations. While WBV experienced a slight decrease of 0.28%, TV remained relatively stable at a 0.07% increase. CGMV exhibited a modest uptick of 0.63%, while MOV and LVV saw minor changes of 0.35% and 1.16%, respectively. These findings highlight the nuanced impact of ozanimod on various brain regions.

Conclusion: ZEPOSIA (ozanimod), an oral medication approved by the FDA for treating adults with RMS, has been shown to greatly decrease the yearly rate of relapses and decrease the percentage of patients experiencing relapses compared to alternative disease-modifying therapies. The comprehensive ozanimod study indicates promising outcomes, showcasing intricate effects on brain regions. ENLIGHTEN’s findings suggest the preservation of key brain structures, offering optimism for RMS management.