The Food and Drug Administration (FDA) has approved Zeposia® (ozanimod; Bristol-Myers Squibb) for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator, binds with high affinity to S1P receptors 1 and 5 and blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood.The mechanism by which it exerts therapeutic effects in MS is unknown but may involve the reduction of lymphocyte migration into the central nervous system.
The approval was based on data from 2 double-blind, parallel-group, active comparator-controlled clinical trials in patients with relapsing forms of MS. Both studies included patients who had experienced at least 1 relapse within the prior year, or 1 relapse within the prior 2 years with evidence of at least a gadolinium-enhancing (GdE) lesion in the prior year, and had an Expanded Disability Status Scale score from 0 to 5.0 at baseline.
Patients were randomized to receive ozanimod 0.92mg given orally once daily, beginning with a dose titration, or interferon beta-1a 30mcg given intramuscularly once weekly. The primary end point of both studies was annualized relapse rate (ARR) over the treatment period.
Results showed that in both trials, the ARR was statistically significantly lower in patients treated with ozanimod than in patients who received interferon beta-1a (Study 1: ARR 0.181 vs 0.350, respectively; Study 2: ARR 0.172 vs 0.276, respectively). Compared with interferon beta-1a, ozanimod demonstrated a relative reduction in ARR of 48% (P<.0001) through 1 year (Study 1) and 38% (P <.0001) at 2 years (Study 2). A similar effect was observed in exploratory subgroups defined by sex, age, prior nonsteroid therapy for MS, and baseline disease activity.
Moreover, the number of new or enlarging T2 hyperintense lesions and the number of GdE lesions were found to be statistically significantly lower in ozanimod-treated patients compared with patients who received interferon beta-1a.
With regard to safety, the most common adverse reactions associated with treatment included upper respiratory tract infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
Ozanimod is contraindicated in patients who in the last 6 months, have experienced a myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure; have the presence of Mobitz type II second degree or third degree atrioventricular block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker; have severe untreated sleep apnea; or are taking a monoamine oxidase inhibitor.
Before initiating therapy, a complete blood count (with lymphocyte count), an electrocardiogram, and liver function tests should be obtained; in patients with a history of uveitis or macular edema, an ophthalmic assessment is required.
Zeposia is supplied in 0.23mg, 0.46mg, 0.92mg strength capsules. According to BMS, commercialization will be delayed due to the COVID-19 pandemic.
For more information visit bms.com.