Background: Omaveloxolone is approved in the US, EU, and Switzerland for the treatment of Friedreich ataxia (FA) in patients aged ≥16 years. Omaveloxolone is not indicated for use during pregnancy or lactation; women of childbearing potential should use effective contraception prior to starting treatment with omaveloxolone, during treatment, and for 28 days following discontinuation. Omaveloxolone showed potential for fetal harm and developmental toxicity in animal studies. Data on omaveloxolone use in pregnant or lactating patients are lacking.
Objectives: To assess the association between omaveloxolone exposure during pregnancy and/or lactation and subsequent maternal, fetal, and infant outcomes.
Methods: The SKYCLARYS® (omaveloxolone) Pregnancy and Lactation Surveillance Program (NCT06628687) is a worldwide, observational, descriptive, phase 4 study. Patients with FA who are exposed to omaveloxolone at any time during pregnancy (from 12 days before conception to pregnancy outcome) and/or lactation (up to 1 year of infant age or weaning, whichever earlier) will be enrolled prospectively (encouraged) or retrospectively (permitted; with baseline/demographic data). The primary outcome is the prevalence of major congenital malformations; secondary outcomes include prevalence of minor congenital malformations, gestational diabetes, preeclampsia, fetal loss, live birth, preterm birth, small for gestational age, neonatal death, infant death, postnatal growth deficiency, infant developmental delay, infant hospitalization due to serious illness, and infant serious or opportunistic infections. Because FA is a rare condition and the label advises against omaveloxolone use during pregnancy and lactation, approximately 10-20 patients are expected to enroll over 10 years for data collection. The analysis population is defined as prospectively enrolled participants with exposure during pregnancy, who meet the minimum criteria for enrollment and have available HCP-confirmed pregnancy or infant outcome data. Data will be collected over 10 years with annual interim analyses. A study limitation is the lack of a comparator group; background rates from population-based surveillance systems and published literature will be referenced and potential biases examined and considered in the interpretation of study results.
Conclusions: This study will inform on maternal, fetal, and infant outcomes following omaveloxolone exposure during pregnancy and/or lactation.