The FDA has approved ozanimod for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. The oral sphingosine-1-phosphate (S1P) receptor modulator will be marketed as Zeposia.1
"With the FDA approval of Zeposia, appropriate patients with relapsing forms of multiple sclerosis will have another oral treatment option with meaningful efficacy to help address the disease’s hallmark relapses and brain lesions," said Samit Hirawat, MD, chief medical officer, Bristol Myers Squibb, in a statement.1 "Zeposia has substantial clinical potential, and we are well positioned with our heritage in transformational science to ensure this innovative compound ultimately benefits as many patients as possible."
Although the drug requires no CYP2C9 genotyping or first-dose observation, it is suggested that an up-titration scheme be employed in order to reach a maintenance dose due to the risk of transient cardiac conduction issues.
The approval of ozanimod was based off data from the phase 3 SUNBEAM (NCT02294058) and RADIANCE part B (NCT01628393) trials that included more than 2600 adults. The randomized, active-controlled studies compared ozanimod to interferon beta-1a (IFNß1a; Avonex) on the primary end point of annualized relapse rate (ARR).
In the SUNBEAM trial, 1346 patients with RMS were randomly assigned to either 1.0 mg (n = 447) or 0.5 mg (n = 451) of ozanimod or IFN-ß1a (n = 448), of which 6.8% (n = 91) of participants discontinued the study drug (1.0 mg group, n = 29; 0.5 mg group, n = 26; IFNß1a group, n = 36). Over a 12-month treatment period, the adjusted ARR were 0.35 (95% CI, 0.28–0.44) for IFN-ß1a compared with 0.18 (95% CI, 0.14–0.24) for the ozanimod 1.0-mg group and 0.24 (95% CI, 0.19–0.31) for the 0.5-mg group, for respective rate ratios of 0.52 (95% CI, 0.41–0.66; P <.0001) and 0.69 (95% CI, 0.55–0.86; P = .0013). The therapy was found to be generally well tolerated, with about 3% of patients treated with the study drug discontinuing due to adverse events (AEs). Serious AEs occurred in 2.9% (n = 13) in the 1.0-mg group, 3.5% (n = 16) in the 0.5-mg group, and 2.5% (n = 11) in the IFN-ß1a group. No serious opportunistic infections occurred in ozanimod-treated participants.2
In addition to reduced ARR, treatment with ozanimod was associated with a 63% relative reduction of T1-weighted gadolinium-enhanced lesions, and a 48% relative reduction in new or enlarging T2 lesions at 1 year in SUNBEAM.2 Similar reductions were observed at 2 years in RADIANCE, as well.3 Notably, there was no significant difference in confirmed disability progression between the 2 study drugs at 3 and 6 months.
Additional analysis on cognitive processing speed showed that compared with IFN-ß1a, ozanimod resulted in sustained improvements through 12 months, with 25% of study participants who showed stability at month 6 also showing improvement at month 12. Among those who demonstrated improvement in the Symbol Digit Modalities Test score at month 6, greater proportions treated with ozanimod 0.5 mg and 1 mg sustained improvement at month 12 than with IFN-ß1a (63% and 66% vs 56%, respectively).2
Ozanimod is contraindicated in patients who have experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III/IV heart failure in the prior 6 months; patients who have a presence of Mobitz type II second or third-degree atrioventricular block, sick sinus syndrome, or sino-atrial, unless the patient has a functioning pacemaker; patients with severe untreated sleep apnea; and patients taking a monoamine oxidase inhibitor.
Treatment with ozanimod may be associated with increased risk of infections, bradyarrhythmia and atrioventricular conduction delays, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, posterior reversible encephalopathy syndrome, additive immunosuppressive effects from prior immune-modulating treatments, severe increase in disability and immune system effects after stopping ozanimod. The most common AEs (incidence ≥4%) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
1. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis [news release]. Briston Myers Squibb Company. March 26, 2020. finance.yahoo.com/news/u-food-drug-administration-approves-103000096.html
2. Comi G, Kappos L, Selmaj KW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomized, minimum 12-month, phase 3 trial. Lancet Neurol. Published online September 3, 2019. doi: 10.1016/S1474-4422(19)30239-X.
3. Cohen JA, Arnold DL, Comi G, 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 Neurol. 2016;15(4):373-381. doi: 10.1016/S1474-4422(16)00018-1.