SUMMIT, N.J.—In a post-hoc analysis of the data from Celgene Corporation's Phase 3 RADIANCE Part B trial, it was demonstrated that ozanimod administration reduced cortical grey matter volume loss in adults with relapsing multiple sclerosis (RMS) compared to first-line treatment Avonex. Celgene is presenting the analysis at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia.
The study compared two doses of oral ozanimod (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg ozanimod HCI, respectively) vs. interferon beta-1a in 1,313 patients with RMS between the ages of 18 and 55 years old. A post-hoc look at the data from the 874 evaluable patients assessed treatment effect on serial brain volume, including thalamic volume and cortical grey matter, based on patient page at baseline, 12 months and 24 months.
The results showed that patients in all age groups in the ozanimod cohort saw less cortical grey matter volume loss than patients treated with interferon beta-1a over 24 months, including patients in the 18 to 25 age group. Such patients tended to have greater brain volume at baseline, but more active disease as measured by gadolinium-enhancing MRI lesions. This age group also tended to see greater whole brain volume loss at 12 and 24 months compared to older groups.
“Brain volume loss is associated with long-term physical disability and cognitive issues in multiple sclerosis,” said Dr. Bruce Cree, Professor of Neurology at the University of California, San Francisco (UCSF) Weill Institute for Neurosciences, Clinical Research Director at the UCSF MS Center, and an author of the analysis. “Ozanimod reduced the loss of cortical grey matter volume across all age groups in this study.”
“Since loss of brain volume can be associated with disease progression, there is a need for early diagnosis and treatment in multiple sclerosis,” added Dr. Alise Reicin, president, Global Clinical Development for Celgene. “This analysis adds to growing evidence supporting the potential use of ozanimod 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.”
The most common adverse reactions (≥ 5 percent) in this trial that were more common in the ozanimod group than with interferon beta-1a were upper respiratory tract infections, urinary tract infections, increases of alanine aminotransferase and increases of gamma-glutamyl transferase.
Ozanimod is an investigational oral, sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity selectively to S1P subtypes 1 (S1P1) and 5 (S1P5). Celgene has submitted a New Drug Application and a Marketing Authorization Application to the FDA and European Medicines Agency, respectively, for ozanimod for the treatment of adults with RMS. The applications were submitted this March.
In multiple sclerosis, the immune system attacks and destroys the myelin sheath surrounding nerves, which leads to disrupted nerve signaling between the brain and the body, and eventually can lead to irreversible nerve deterioration. Roughly 400,000 individuals in the United States are afflicted with multiple sclerosis, and roughly 2.5 million individuals worldwide. RMS features defined attacks of worsening neurologic function, in which flare-ups are followed by partial or complete remissions. Approximately 85 percent of patients are initially diagnosed with RMS.
SOURCE: Celgene Corporation press release