GFAP Biomarker Analysis Shows Ozanimod's Impact on MS Disease Progression in ENLIGHTEN Trial
Key Insights
Interim analysis of ENLIGHTEN trial reveals ozanimod treatment reduced mean GFAP concentration from 115.0 to 103.2 pg/mL over one year in relapsing multiple sclerosis (search) patients.
GFAP levels showed significant correlations with various MRI parameters, including positive associations with lesion volumes and negative correlations with brain volume measures.
Patients demonstrated cognitive improvements with ozanimod treatment, with 48.1% achieving clinically meaningful improvement in SDMT scores after one year.
New findings from the phase 3 ENLIGHTEN trial demonstrate that ozanimod treatment leads to improved biomarker levels and slower disease progression in patients with early relapsing multiple sclerosis (search), according to data presented at the 2025 ACTRIMS Forum in West Palm Beach, Florida.
The interim analysis, led by Dr. Sarah A. Morrow from the University of Western Ontario, examined 162 patients with GFAP and MRI data, revealing significant correlations between biomarker levels and disease progression markers. After one year of treatment with 0.92 mg ozanimod, patients showed notable improvements in multiple disease measures.
Biomarker and Imaging Correlations
The study demonstrated a reduction in mean GFAP concentration from 115.0 pg/mL at baseline to 103.2 pg/mL after one year of treatment. Baseline GFAP levels showed significant positive correlations with several MRI parameters, including:
- T1 lesion count (P = .030)
- T1 hypointense lesion volume (P = .34)
- T2 lesion count (P = .22)
- T2 hyperintense lesion volume (P = .32)
- Lesional ventricular volume (P = .032)
Notably, negative correlations were observed with cortical grey matter volume and thalamic volume, suggesting a relationship between GFAP levels and neurodegeneration.
Patient Demographics and Treatment Response
The study population comprised predominantly treatment-naïve patients (68%), with a mean age of 39.7 years and an average of 4.0 years since MS onset. The mean number of relapses in the year prior to treatment was 0.75, indicating active disease.
Changes in GFAP levels over the one-year treatment period showed positive correlation with gadolinium-enhancing lesion volume changes and negative correlation with lesional ventricular volume, suggesting ozanimod's effectiveness in controlling disease activity.
Cognitive Function Improvements
The trial also assessed cognitive function through multiple standardized tests. Key findings included:
- 9.6% mean improvement in Symbol Digits Modalities Test (SDMT) scores
- 6.2% improvement in California Verbal Learning Test Second Edition (CVLT-II) scores
- 3.7% improvement in Brief Visuospatial Memory Test-Revised (BVMT-R) scores
Particularly noteworthy was that 48.1% of patients achieved clinically meaningful improvement in SDMT scores, demonstrating ozanimod's potential impact on cognitive function.
Mechanism of Action and Clinical Implications
Ozanimod, a sphingosine 1-phosphate receptor (search) modulator, works by preventing lymphocytes from entering the bloodstream from lymph nodes. Its selective receptor targeting profile contributes to a favorable safety profile compared to earlier generation S1P modulators.
The drug's once-daily oral administration and established safety profile, combined with these positive biomarker and cognitive function results, further support its role in the treatment of relapsing multiple sclerosis (search). These findings provide valuable insights into the relationship between biomarker levels and disease progression, potentially offering new ways to monitor treatment response in MS patients.