Zeposia (ozanimod) is a sphingosine-1-phosphate (S1P) receptor modulator, taken orally once daily and is indicated for relapsing-remitting MS. Zeposia works by entering the central nervous system (CNS) and binds to specific subtypes of the sphingosine 1-phosphate (S1P) receptor, S1P1R and S1P5R. 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 from being activated and released from the lymph nodes and thymus gland into the blood circulation and, hence, the brain and spinal cord. Zeposia differs from other S1P receptor modulators on the market as it follows a drug titration regimen (gradual increased dosing) and does not require first dose-monitoring for a reduction in heart rate.
Health Canada’s approval is based on two phase three trials, RADIANCE and SUNBEAM.
RADIANCE was a combined phase II/III randomized, double-blind placebo-controlled clinical trial to assess 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 received 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, 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 trials, a very low rate of disability progression was observed across the treatment groups, though ozanimod did not reach statistical significance compared to Avonex®.
The MS Society will provide updates related to reimbursement as they become available. Individuals interested in treatment with ozanimod are encouraged to speak with their MS healthcare team.
References:
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.
Comi G, Kappos L, Selmaj KW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009-1020.