- Brand name: RPC-1063(Celgene)
- Route of Administration: Oral (0.5 mg or 1 mg daily)
- Type: Sphingosine-1-phosphate (S1P) receptor modulator; immunomodulator
- Status: Completed Phase III clinical trial
Belonging to the same class of drugs as fingolimod (Gilenya) and siponimod, ozanimod reduced the annualized relapse rate in phase III clinical trials involving people living with relapsing-remitting MS.
How it Works
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.
Research and Results
A phase II randomized, double-blind placebo-controlled clinical trial called RADIANCE tested the safety and efficacy of ozanimod in 258 individuals with relapsing-remitting MS. 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 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.
Another phase III randomized, double-blind clinical trial has been conducted. SUNBEAM 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 relapsing-remitting MS across 152 sites and 20 countries. The clinical trial met its primary endpoint of reducing annualized relapse rates compared to interferon beta-1a. In addition, treatment with ozanimod resulted in reduced the number of 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®.
A New Drug Application submission to the U.S. Food and Drug Administration, based on the combined SUNBEAM and RADIANCE trials for RMS, is expected by the end of 2017.
Adverse Effects Reported
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, which include more individuals with MS. The MS Society will report any new adverse effects that are disclosed from the 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.