Background

Ozanimod is a potent, orally bioavailable, sphingosine 1-phosphate (S1P) receptor modulator, which binds with high affinity selectively to S1P receptor subtypes 1 and 5. Ozanimod was recently approved in the US and EU for the treatment of relapsing forms of multiple sclerosis.

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 known to be involved in vascular formation during embryogenesis. In the clinical development program for ozanimod, female 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.

Objectives

To review the pregnancy outcomes data in the ozanimod clinical development program in relapsing multiple sclerosis.

Methods

Pregnancy outcomes were assessed in cases reported from all multiple sclerosis studies in the ozanimod clinical development program and diagnosed by December 31, 2019. Pregnancy outcomes through June 15, 2020 are reported.

Results

Forty-two pregnancies were reported among 1868 female ozanimod-treated participants with multiple sclerosis. Outcomes include 26 live births, including 20 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 (of which 1 was a loss of a twin), 9 elective terminations, 1 pregnancy ongoing, 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% to 22%; García-Enguídanos et al 2002).

Conclusions

While there has been limited clinical experience with ozanimod during pregnancy, and pregnancy should be avoided while taking and for 3 months after stopping ozanimod, to date there has been no signal of an increased risk of fetal abnormalities or other adverse pregnancy outcomes seen with exposure in early pregnancy.