New Post-Marketing Study to Test Omaveloxolone in Pregnant and Lactating Patients

Author(s):

This phase 4 study on omaveloxolone will assess long-term maternal and infant health, potentially informing future safety guidelines for patients with Friedreich ataxia.

Jennifer Farmer, MS

Investigators have unveiled the design of a new post-marketing observational study (NCT06628687) assessing maternal, fetal, and infant outcomes following omaveloxolone (Skyclarys; Biogen) exposure during pregnancy and/or lactation. Omaveloxolone, a nuclear factor-like 2 activator, is the only therapy FDA-approved for adults with Friedreich ataxia (FA).¹

This descriptive, phase 4 study is expected to include 10-20 participants, aged at least 16 years, who’ve had exposure to omaveloxolone at any time during pregnancy (from 12 days prior to conception to pregnancy outcome) and/or during lactation (up to 1 year of infant age or weaning, whichever comes first). The study will use prevalence of major congenital malformations, observed up to 10 years, as the primary study outcome, with other secondary outcomes that include minor congenital malformations, neonatal death, gestational diabetes, and others.

The design of the study was presented as a poster by Jennifer Farmer, MS, chief executive officer of the Friedreich’s Ataxia Research Alliance, at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific conference, held March 16-19 in Dallas, Texas. Data for the study will be collected from enrolled pregnant or lactating individuals or the healthcare providers (HCP) involved in their care or the care of their infants. The surveillance program is strictly observational, with the schedule of office visits and all treatment regimens determined by the participants attending HCP. Conducted across several centers worldwide, the study is planned to end no earlier than April 2035 after 10 years of data collection, with annual interim analyses.

Other secondary outcomes from the study include observing infant death, preeclampsia, postnatal growth deficiency and infant developmental delay, fetal loss, live birth, preterm birth, infant hospitalization, serious or opportunistic infections, and small for gestational age. For analyses of the outcomes of preterm birth, small form gestational age, and postnatal growth deficiency, participants with multiple gestational pregnancies will be excluded from the analysis population. Retrospectively enrolled participants, participants excluded during lactation only, and participants with only patient-reported data will be included in supplementary analyses of outcomes.

Omaveloxolone, approved in 2022, is not indicated for use during pregnancy or lactation. In preclinical animal studies, the therapy has shown potential for fetal harm and developmental toxicity at plasma exposures similar to or less than exposures in humans. Currently, no data exist on the presence of omaveloxolone or its metabolites in human milk, and the effects on milk production and breastfed infants are unknown.

Patients may be identified to enter the study through other existing registries like SKYCLARYS PASS (NCT06623890) and the FARA/Friedreich Ataxia Global Clinical Consortium Unified Natural History Study. SKYCLARYS PASS, announced at the 2024 International Congress for Ataxia Research, is a postmarketing registry that collects long-term safety and patient experience data on omaveloxolone. The hope is that through the registry, which will follow omaveloxolone-naïve patients for up to 5 years, findings will help guide healthcare professionals in their clinical decisions.²

SKYCARYS PASS combines both the Friedreich Ataxia Clinical Outcome Measures Study (FACOMS) and the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS). FACOMS, originally created in 2004, includes over 1000 patients with FA across Australia, Canada, India, New Zealand, and the USA. EFACTS, which has been around since 2013, includes more than 1000 patients from Belgium, Czech Republic, France, Germany, Greece, Ireland, Italy, Spain, and the United Kingdom.

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REFERENCES
1. Farmer J, Dobay P, Domingo-Horne RM, et al. Treatment of Friedreich Ataxia With Omaveloxolone During Pregnancy and/or Lactation: Design and Rationale of a Post-Marketing Observational Study. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-19; Dallas, TX. ABSTRACT P180.
2. Perlman S, Lynch D, Mariotti C, et al. Study design of an observational, multinational, postmarketing registry of omaveloxolone-treated patients with Friedreich ataxia. Presented at: International Congress for Ataxia Research (ICAR) 2024; November 12-15; London, UK