Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, which binds with high affinity selectively to S1P receptor subtypes 1 and 5, was recently approved in the US and EU for the treatment of RMS.

Nonclinical reproductive safety assessments with S1P modulators in rats and rabbits have shown embryo-fetal toxicity, including embryo-fetal deaths and visceral malformations. The S1P receptor is involved in vascular formation during embryogenesis. Female clinical trial participants of childbearing potential are required to use effective contraception while receiving and up to 3 months after discontinuing ozanimod and to discontinue ozanimod if pregnancy is confirmed.

Forty-two pregnancies were reported among 1868 female ozanimod-treated participants with RMS. Outcomes include 27 live births, including 21 normal and 3 premature but normal infants, 1 report each of neonatal icterus, late intrauterine growth retardation with subsequent normal progress over the first year, and duplex kidney (common variant in 1.8% of births). There were 6 early spontaneous abortions (1 was a loss of a twin), 9 elective terminations, and 1 subject refused consent to follow-up. The incidence of spontaneous abortion in clinical trial participants exposed to ozanimod (6/43, 14%) is at the lower end of the expected rate of early pregnancy loss in the general population (12%?22%).