Ozanimod (Zeposia), an oral sphingosine-1-phosphate (S1P) receptor modulator, won FDA approval to treat relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, Bristol Myers Squibb .
The approval came 2 years after the the drug's original application, saying drugmaker Celgene (now part of Bristol Myers Squibb) did not provide enough pharmacology information. The product will be delayed again, this time by the company.
"As the country's healthcare system is dealing with the unprecedented COVID-19 pandemic, Bristol Myers Squibb has made the decision to delay commercialization of Zeposia," a company press release announced. "Bristol-Myers Squibb will continue to monitor the environment and will partner with the neurology community to inform launch timing."
The FDA decision was based on data from the and studies comparing ozanimod against interferon beta-1a (Avonex). showed the adjusted annual relapse rate (ARR) at 1 year for ozanimod 1 mg was 0.18, versus 0.35 for interferon beta-1a. In , adjusted ARRs at 2 years were 0.17 for ozanimod 1 mg and 0.28 for interferon beta-1a. The numbers of gadolinium-enhanced brain lesions and new or enlarging T2 lesions also were reduced with ozanimod in these trials. No statistically significant difference in 3-month or 6-month confirmed disability progression was found between the ozanimod and interferon beta-1a groups.
In the trials, ozanimod showed "acceptable safety and tolerability," Bristol Myers Squibb said. The most common adverse reactions (incidence of 4% or greater) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension. Herpes zoster was reported as an adverse reaction in ozanimod-treated patients.
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 last 6 months. The drug is also contraindicated in patients who have a Mobitz type II second- or third-degree atrioventricular block, sick sinus syndrome, or sino-atrial block unless the patient has a functioning pacemaker, and in patients with severe untreated sleep apnea or who are taking a monoamine oxidase inhibitor.
The drug carries a warning for 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 after stopping treatment, and immune system effects after stopping treatment.
Ozanimod is an oral S1P receptor modulator which binds selectively to S1P subtypes 1 and 5. A once-daily 0.92 mg capsule, ozanimod does not require patients to get genetic testing before starting the drug or to be observed after getting their first dose, Bristol Myers Squibb said. Up-titration should be used to reach the maintenance dosage of the drug because a transient decrease in heart rate and atrioventricular conduction delays may occur, the company added. More about ozanimod can be found in the full and the .