Analysis: Oral Ozanimod Reduces Brain Volume Loss in Relapsing MS

Compared with interferon beta-1a, ozanimod reduced less cortical grey matter volume in patients with relapsing forms of multiple sclerosis.

Oral ozanimod reduced cortical grey matter volume loss in all patient age groups with relapsing multiple sclerosis (RMS), according to new data from a post-hoc analysis of the RADIANCE Part B clinical trial.

The findings were presented at the 2019 American Academy of Neurology Annual Meeting.

Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is currently in development for immune-inflammatory indications, including RMS, ulcerative colitis, and Crohn disease. In March, Celgene submitted a new drug application to the FDA seeking approval for the drug as a treatment for adults with RMS, which included data from the SUNBEAM and RADIANCE Part B phase 3 clinical trials.

In the RADIANCE Part B trial, investigators evaluated 2 doses of oral ozanimod (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg ozanimod HCl, respectively) in comparison with weekly intramuscular interferon beta-1a (Avonex) in 1313 patients with RMS over a 24-month period. The primary endpoint of the study was annualized relapse rates (ARRs) over the treatment period.

In the post-hoc analysis, treatment effect on serial brain volume, including thalamic volume and cortical grew matter, was evaluated in 874 patients by age. The study showed that patients in the 18 to 25 age group tended to have greater brain volume at baseline, but more active disease as measured by gadolinium-enhancing MRI lesions. This age group also demonstrated greater whole brain volume loss at both 12 and 24 months compared with the older age groups.

Overall, patients across all age groups treated with ozanimod lost less cortical grey matter volume than those treated with interferon beta-1a over 24 months, including those in the 18 to 25 age group, according to the analysis.

“Since loss of brain volume can be associated with disease progression, there is a need for early diagnosis and treatment in multiple sclerosis,” Alise Reicin, MD, president of Global Clinical Development for Celgene, said in a statement. “This analysis adds to growing evidence supporting the potential use of ozanimoid to treat adults with relapsing multiple sclerosis, including the youngest patients studied, who also showed the most rapid loss in brain volume in this study.”

Previously reported findings from the RADIANCE trial showed a significant reduction in ARR for ozanimod 1 mg and ozanimod 0.5 mg compared with interferon beta-1a. The most common adverse reactions with ozanimod were upper respiratory infection, urinary tract infections, increases of alanine aminotransferase, and increase of gamma-glutamyl transferase.

Ozanimod works by binding with high affinity selectively to S1P subtypes 1 and 5 and causes lymphocyte retention in lymphoid tissues. According to Celgene, the mechanism by which ozanimod exerts therapeutic effect in MS is unknown but may involve the reduction of lymphocyte migration into the central nervous system.

Reference

Analysis Showed Oral Ozanimod Reduced Brain Volume Loss Across All Age Subgroups in Adults with Relapsing Multiple Sclerosis [news release]. Celgene. https://ir.celgene.com/press-releases/press-release-details/2019/Analysis-Showed-Oral-Ozanimod-Reduced-Brain-Volume-Loss-Across-All-Age-Subgroups-in-Adults-with-Relapsing-Multiple-Sclerosis/default.aspx. Accessed May 10, 2019.