Ozanimod (formerly RPC1063) is an investigational, oral, selective sphingosine 1-phosphate (S1PR1) and 5 (S1PR5) receptor modulator now in advanced Phase 3 testing as a potential treatment for relapsing-remitting multiple sclerosis (RRMS). It is also in development for ulcerative colitis and Crohn’s disease.
S1PR1 receptor modulators interfere with S1P signaling. They block lymphocytes (immune cells) from receiving exit signals inside the lymph nodes. This keeps the immune cells trapped inside the node. The result is a reduction of circulating T- and B-cells, leading to anti-inflammatory activity because the drug stops the migration of certain immune cells to the actual sites of inflammation.
Researchers believe that selective binding with S1PR5 receptors activates specific cells within the brain and spinal cord, which have the potential to enhance remyelination and prevent synaptic defects. Ultimately, neurological damage may be prevented.
Studies involving ozanimod
In September 2016, Celgene, the company developing ozanimod, announced positive results from its Phase 2 RADIANCE study (NCT01628393). Findings demonstrated that ozanimod was effective in reducing total brain lesions, as determined by magnetic resonance imaging (MRI) scans, after 24 weeks of treatment. Results of a nearly two-year safety and efficacy extension study further emphasized the potential of ozanimod to treat RRMS.
Common side effects reported in treated patients were mostly minor infections (nasopharyngitis, respiratory tract and urinary tract infections ) and headache, with no reports of new safety or tolerability issues.
This trial (NCT02047734) evaluated the efficacy, safety, and tolerability of two oral doses of ozanimod (0.5 mg and 1 mg) against weekly intramuscular interferon beta-1a (Avonex) and placebo in approximately 1,200 RRMS patients over 24 months of treatment.
Both ozanimod doses met the study’s primary endpoint of reducing annualized relapse rates. Key secondary goals regarding the number of new or enlarging T2 MRI lesions and the number of gadolinium-enhancing MRI lesions after the 24-month treatment period were also met. (Gadolinium is a large molecule that only crosses the blood-brain barrier when inflammation exists. In an MRI, gadolinium is used as a contrast material to highlight new and active areas of inflammation.)
Another Phase 3 trial called SUNBEAM (NCT02294058) finished in December 2016, and topline data were released in February 2017. The randomized, double-blind study compared the safety and effectiveness of oral ozanimod (0.5 mg and 1 mg doses) with Avonex in 1,346 RRMS patients.
Results showed that treatment with ozanimod — at either dose — produced both statistically significant and clinically meaningful improvements in treated patients in the trial’s primary goal of lower annualized relapse rates, compared to those given Avonex. Ozanimod-treated patients also showed significant and meaningful improvements in the trial’s secondary objectives: fewer gadolinium-enhancing MRI lesions and new or enlarging T2 MRI lesions at month 12, and again at month 24.
A pre-specified analysis of time to onset of disability progression was also conducted, in an agreement with the FDA under the protocol assessment, using pooled results from both the SUNBEAM and RADIANCE Phase 3 trials. A very low rate of disability progression in all three treatment groups was observed — ozanimod and Avonex — meaning ozanimod was not significantly superior to Avonex. But the Phase 3 trials did show that ozanimod, at both 0.5 mg and 1 mg, significantly reduced brain atrophy compared to Avonex.
A new Phase 3 (NCT02576717) open-label extension study is now recruiting RRMS patients who participated in earlier ozanimod trials, an estimated 2,350 people, to further evaluate the treatment’s safety and efficacy. This trial is expected to run through mid-2020, but may end earlier should Celgene discontinue ozanimod’s development program.
Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.