Pregnancy Outcomes in the Ozanimod Clinical Development Program in Relapsing Multiple Sclerosis, Ulcerative Colitis, and Crohn’s Disease

Background: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in the US for the treatment of relapsing multiple sclerosis (RMS) and in Canada and the EU for the treatment of relapsing-remitting MS. Ozanimod has demonstrated efficacy in patients with ulcerative colitis (UC) and is being studied in Crohn’s disease (CD). S1P1-3 receptors are involved in vascular formation during embryogenesis. Within studies in the ozanimod clinical development program, female participants of childbearing potential were required to use effective contraception while receiving and up to 3 months after discontinuing ozanimod; treatment discontinuation was required if pregnancy was confirmed. Objectives: To review pregnancy outcomes data with ozanimod use in RMS, UC, and CD. Methods: All participant and partner pregnancies in the ozanimod clinical development program with an initial diagnosis prior to September 30, 2020 were assessed for pregnancy outcomes. Results: A total of 83 participant or partner pregnancies were reported in the safety database. All pregnancy exposures occurred during the first trimester. Of the 60 participant pregnancies in ozanimod clinical trials, 47 were in participants with RMS, 9 with UC, 3 with CD, and 1 healthy volunteer. Participants discontinued study medication promptly, except for those who elected pregnancy termination and remained on study medication. The incidence of spontaneous abortion in clinical trial participants was 15%; the rate in the general population is between 12% and 22%. The rate of preterm birth was 10.7% of live births; the global population estimate is 10.6% and the European estimate is 8.7%. Outcomes in patients with RMS included 25 live births (2 with congenital abnormalities [duplex kidney, congenital hydrocele]), 3 premature births, 2 ongoing pregnancies, 7 spontaneous early losses (1 loss of a twin), 9 elective terminations, and 2 with no information provided to date, despite follow-up. No teratogenicity was observed. Conclusions: While pregnancy should be avoided in patients on and for 3 months after stopping ozanimod and clinical experience with ozanimod during pregnancy is limited, there has been no increased event of fetal abnormalities or adverse pregnancy outcomes seen with ozanimod exposure in early pregnancy in a small cohort of patients.

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