HOW DOES THIS TREATMENT WORK?
Two-Minute Mechanism Video: Omaveloxolone
This short video explains how omaveloxolone works to potentially provide benefit to someone with FA.
Improve Mitochondrial Function & Reduce Oxidative Stress
SKYCLARYS (omaveloxolone)
Biogen
Available to patients *
Omaveloxolone (aka omav), brand name SKYCLARYS™, was originally developed by Reata Pharmaceuticals and then purchased by Biogen. On February 28, 2023, the United States Food & Drug Administration (FDA) approved SKYCLARYS™ in FA for people 16 years of age and older. This marks a milestone for the FA community- the first approved treatment for FA. Its proposed mechanism of action is activation of a transcriptional factor Nrf2, which was shown by researchers (e.g., Gino Cortopassi, UC Davis, Paola Giunti, UCL, and Pierre Rustin, France) to be paradoxically decreased in cells from FA patients. Increasing Nrf2 could improve mitochondrial function by reducing oxidative stress and preventing lipid peroxidation. In preclinical studies omav and other Nrf2 activator compounds were shown to increase the number of mitochondria, improve mitochondrial efficiency, boost energy production by mitochondria, and reduce lipid peroxidation.
* The drug is approved for use in the US and the EU for people with FA greater than 16 years of age. Additional clinical studies are underway to support the approval of use in people with FA younger than 16 years of age.
What is the status of development?
History of Development for SKYCLARYS
The drug development process can be thought of as a series of stages, and successful drugs must pass through each stage to become available to patients.
Several academic research labs demonstrated in both human FA cell models and mouse models that Nrf2 is downregulated. In addition, treatment of FA cell and animal models with omavoloxone demonstrated activation of Nrf2 and improvements in the mitochondrial function. Studies have shown that treatment with omav reduced pathologic levels of oxidative stress, restored antioxidative response, restored complex 1 activity, decreased lipid peroxidation, and decreased mitochondrial reactive oxygen species (ROS). In cellular assays, omav prevented cell death following pro-oxidant challenge. See links to published papers to learn more about these studies.
Working with FARA and several FA Investigators in our Collaborative Clinical Research Network (CCRN), Reata conducted a two-part, randomized, placebo-controlled Phase 2/3 Study of the Safety, Efficacy, and Pharmacodynamics of omav. Part 1 of the study was a randomized, placebo-controlled, double-blind, dose-escalation study. Part 2 of the study was conducted to establish the longer-term effectiveness of omav. Finally, Reata also conducted an open label extension study. People who participated in MOXIe part 1 or 2 were able to take omav and continue to be followed for assessment of both efficacy and safety.
May 20, 2024: Biogen initiated an open-label study evaluating the safety, tolerability, and pharmacokinetics (PK) of omaveloxolone following single dose administration in pediatric patients with FA.
The first study cohort included participants who are 12 to 15 years old with genetically confirmed FA.
September 13, 2024: The study team recruited participants for two cohorts with a genetically confirmed FA diagnosis between the ages of 6-11 years old and 12-15 years old. Parents/caregivers contacted the study team to put their child’s name on a list of interested participants. Participants were randomly selected from a list for invitation to screen for the study.
Recruitment information for younger cohorts (between ages 2-5 years) will be announced at a later date.
February 28, 2023: Reata Pharmaceuticals announced that the United States Food & Drug Administration (FDA) has approved their New Drug Application (NDA) for SKYCLARYS™ (aka omaveloxolone or omav) in FA for people 16 years of age and older. This marks a milestone for the FA community- the first approved treatment for FA.
February 12, 2024: Biogen Inc. announced the European Commission (EC) has authorized SKYCLARYS® (omaveloxolone) for the treatment of Friedreich’s ataxia (FA) in adults and adolescents aged 16 years and older. SKYCLARYS is the first treatment approved within the European Union for this rare, genetic, progressive neurodegenerative disease.
October 2, 2024:
In this study, researchers will learn more about the safety of BIIB141, also known as omaveloxolone or SKYCLARYS®. This is a drug available for doctors to prescribe for people with Friedreich’s Ataxia (FA). This is known as an “observational” study, which collects health information about study participants without changing their medical care. Participants for this study will be found using the Friedreich’s Ataxia Global Clinical Consortium (FA GCC). This is a group of study research centers that help provide clinical care for people with FA.
October 18, 2024:
SKYCLARYS® (Omaveloxolone) Pregnancy and Lactation Surveillance Program
A Post-Marketing, Observational, Descriptive Study to Assess the Risk of Pregnancy and Maternal Complications and Adverse Effects on the Developing Fetus, Neonate, and Infant Among Individuals Exposed to Omaveloxolone During Pregnancy and/or Lactation
The primary objective of the study is to assess the risks associated with pregnancy and maternal complications in women with Friedreich’s Ataxia (FA) exposed to omaveloxolone during pregnancy and/or lactation. The secondary objective is to assess the adverse effects on the developing fetus, neonate, and infant in women exposed to omaveloxolone during pregnancy and/or lactation.
