Ozanimod (formerly RPC1063) is an investigational, oral, selective sphingosine 1-phosphate (S1PR1) and 5 (S1PR5) receptor modulator currently in development for people with relapsing-remitting multiple sclerosis (RRMS) or 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, which 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 it stops the migration of certain immune cells to the actual sites of inflammation.
Researchers believe that selective binding with S1PR5 receptors activate specific cells within the CNS, which has the potential to enhance remyelination and prevent synaptic defects. Ultimately, neurological damage may be prevented.
Studies Involving Ozanimod
In early September, Ozanimod developer Celgene announced positive results from its Phase 2 RADIANCE study (NCT01628393). The study demonstrated that ozanimod was effective because it reduced total brain lesions, as determined by MRI scans. The results of the 2-year safety and effectiveness study further emphasized the potential of ozanimod to provide a new oral therapeutic option for people with RRMS.
Study participants experienced three serious adverse effects — optic neuritis, unexplained pain, and cellular changes to the cervix — but the effects were not proven to be related to the therapy. Other reactions included headaches, urinary tract infections, and an initial heart rate increase.
The Phase 3 portion of the RADIANCE study began in 2013 by Receptos (now owned by Celgene) under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). The ongoing Phase 3 portion (NCT02047734) compares 0.5 mg and 1.0 mg of ozanimod against interferon beta-1a (Avonex) in approximately 1,200 RRMS patients.
Another Phase 3 trial, SUNBEAM (NCT02294058) has been completed in February 2017. The randomized, double-blind study compared 0.5 mg and 1.0 mg of oral ozanimod against interferon beta-1a (Avonex) in 1,346 people with RRMS. Ozanimod met the primary objective of the study, reducing annualized relapse rate (ARR), compared to weekly interferon (IFN) beta-1a (Avonex).
Results show that treatment with ozanimod 1 mg and 0.5 mg showed statistically significant and clinically meaningful improvements compared to Avonex for the primary objective of ARR and the measured secondary objectives of the number of gadolinium-enhancing MRI lesions and the number of new or enlarging T2 MRI lesions at month 12. A pre-specified analysis on the time to onset of disability progression will be conducted using pooled results from both the SUNBEAM and RADIANCE phase III trials, as agreed to in the Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration.
Celgene announced intention to submit new drug application (NDA) in 2017.
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