P4342 - Pregnancy Outcomes in the Etrasimod Clinical Program

Krisztina B. Gecse, MD, PhD¹, Maria Chaparro, MD, PhD², Maria T. Abreu, MD³, Yvette Leung, MD⁴, Elena Sonnenberg, MD⁵, Aoibhinn McDonnell, PhD⁶, Krisztina Lazin, MD⁷, Joseph Wu, PhD⁸, Christina C. Smith, PharmD, MBA⁹, Márjori Dulcine, MD, MSc¹⁰, Karolina Wosik, MSc, PhD¹¹, Uma Mahadevan, MD^12
1Amsterdam University Medical Center, Amsterdam, Noord-Holland, Netherlands; ²Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigacíon Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Diego de León, Madrid, Spain; ³Crohn's and Colitis Center, University of Miami Miller School of Medicine, Miami, FL; ⁴University of British Columbia, Vancouver, BC, Canada; ⁵Medizinische Klinik m. S. Gastroenterologie, Infektiologie und Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Berlin, Germany; ⁶Pfizer Ltd., Sandwich, England, United Kingdom; ⁷Pfizer AG, Zürich, Zurich, Switzerland; ⁸Pfizer Inc., Cambridge, MA; ⁹Pfizer Inc., Collegeville, PA; ¹⁰Pfizer Brazil, São Paulo, Sao Paulo, Brazil; ¹¹Pfizer Canada, Kirkland, PQ, Canada; ¹²Colitis and Crohn’s Disease Center, University of California San Francisco, San Francisco, CA

Introduction: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC) and in development for the treatment of other immune-mediated inflammatory diseases. Based on animal studies at clinically relevant doses, etrasimod may cross the placenta and cause fetal harm. This analysis describes pregnancy outcomes in patients with maternal or paternal exposure to etrasimod during its clinical development.

Methods: Reports of pregnancy or partner pregnancy during etrasimod exposure were identified from all phase 1–3 completed or ongoing open-label studies up to October 31, 2023. These studies included healthy volunteers or patients with UC, Crohn’s disease, atopic dermatitis, eosinophilic esophagitis, or alopecia areata. In all studies, pregnancy was an exclusion criterion, women of childbearing age were required to use contraception and study drug was discontinued in any female patient that became pregnant. Pregnancy outcomes were categorized as healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or lost to follow-up.

Results: In total, 2,091 unique patients were exposed to etrasimod in clinical trials; 593 (28.4%) were females of childbearing age (aged 16–44). There was a total of 14 pregnancies with exposure to etrasimod (nine maternal, five paternal). All pregnancy exposures were limited to the first trimester. Median (range) age of women with maternal etrasimod exposure was 28.0 (18–36) years. Estimated length of maternal etrasimod exposure (from last menstrual period until last etrasimod dose) ranged from 22 to 79 days. Of the nine maternal exposures, pregnancy outcomes were two healthy newborns, four medical terminations (two for unknown reasons, one due to an anembryonic gestation, and one following “signs of a missed pregnancy”), and one each resulting in a congenital malformation (open [patent] foramen ovale) spontaneous abortion and loss to follow-up (Table). Of the five paternal exposures, there were two healthy newborns, two spontaneous abortions, and one lost to follow-up (Table).

Discussion: Few pregnancies have been reported in the etrasimod clinical program, with no clear trends on the risk of maternal or paternal etrasimod exposure. Ongoing etrasimod studies and larger post-marketing registries will further inform on the safety of etrasimod during pregnancy. Women of child-bearing potential should use birth control while on etrasimod.


Disclosures:


Krisztina B. Gecse, MD, PhD¹, Maria Chaparro, MD, PhD², Maria T. Abreu, MD³, Yvette Leung, MD⁴, Elena Sonnenberg, MD⁵, Aoibhinn McDonnell, PhD⁶, Krisztina Lazin, MD⁷, Joseph Wu, PhD⁸, Christina C. Smith, PharmD, MBA⁹, Márjori Dulcine, MD, MSc¹⁰, Karolina Wosik, MSc, PhD¹¹, Uma Mahadevan, MD¹². P4342 - Pregnancy Outcomes in the Etrasimod Clinical Program, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.