Ozanimod (also known as RPC-1063) works by entering the central nervous system (CNS) and binding to specific subtypes (S1P1R and S1P5R) of the sphingosine 1-phosphate (S1P) receptor. The S1P receptor is found on the surface of specific immune cells called T cells and B cells that play a role in causing damage to the CNS in MS. By binding to the S1P receptor, ozanimod prevents these harmful immune cells – specifically B cells and T cells – from being activated and released from the lymph nodes and thymus gland into the blood circulation and, hence, the brain and spinal cord. Ozanimod is shown to reduce inflammation in animal models of MS.
RADIANCE: Phase II/III Trial
A phase II randomized, double-blind placebo-controlled clinical trial called RADIANCE tested the safety and efficacy of ozanimod in 258 individuals with RRMS. Participants were given oral ozanimod (0.5 mg or 1mg) daily, or a placebo for 24-weeks. RADIANCE met its primary endpoint of reduced number of lesions between weeks 12 and 24 of ozanimod treatment at both dosages. Secondary imaging outcomes including the number of lesions and new or enlarging lesions at 24 weeks were also reduced with ozanimod treatment compared to placebo. The RADIANCE clinical trial was extended to a phase III trial that recruited 1,313 individuals at 147 sites in 21 countries. Participants were administered either ozanimod (0.5 mg or 1mg) daily, a weekly injection of interferon beta-1a (Avonex), or placebo for two years. Both doses of ozanimod met the primary endpoint which was a reduction in the annualized relapse rate compared to interferon beta-1a.
SUNBEAM: Phase III Trial
SUNBEAM, a phase III randomized, double-blind clinical trial, assessed the efficacy, and safety of ozanimod (0.5 mg or 1mg) compared to interferon beta-1a over the course of 12-months.Researchers recruited 1,346 individuals with RRMS across 152 sites and 20 countries. The clinical trial met its primary endpoint of reducing annualized relapse rates compared with interferon beta-1a. Treatment with ozanimod also resulted in less new and enlarging lesions compared to interferon beta-1a.
In a pre-specified pooled analysis of the time to confirmed disability progression in both the RADIANCE and SUNBEAM phase III trials, a very low rate of disability progression was observed across the treatment groups, and ozanimod did not reach statistical significance compared to Avonex®.
Celgene is running a phase III open-label extension study with individuals that participated in earlier ozanimod trials. Therefore, participants can continue taking ozanimod for an additional five years. The long-term adverse effects from this extension study will be reported in mid-2020.
The U.S. Food and Drug Administration (FDA) rejected Celgene’s new drug application for ozanimod as a treatment for people with RRMS based on insufficient data required for a new drug review.
In the phase II RADIANCE clinical trial, the most common adverse effects were headache, nasopharyngitis (inflammation of the nose and pharynx), urinary tract infections, and upper respiratory tract infections. More information on the side effects will be available from the phase III trials. Celgene reported the safety of the SUNBEAM clinical trial was consistent with the safety reported in the RADIANCE trial. The MS Society will report any new adverse effects that are disclosed from the phase III SUNBEAM and RADIANCE when information is available.
Cohen J et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet. 2016; 15(4): 373-81.