Skyclarys (omaveloxolone) / Biogen - LARVOL DELTA

Dual promoter architecture of NFE2L2 underlies isoform-specific translational control of NRF2. (PubMed, Redox Biol) - "The extended P2-specific 5'UTR contains evolutionarily conserved structural features that may contribute to translational regulation. Finally, the electrophilic NRF2 activator omaveloxolone (RTA-408) induced translation of transcripts from both promoters, demonstrating that NRF2 stress response is coordinated through the combined regulation of mRNA translation and protein stability."

Journal • Oncology • KEAP1

Omaveloxolone in a real-world setting: implications in Friedreich Ataxia beyond the classic study population (MDS Congress 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Ataxia • CNS Disorders • Movement Disorders

A Study to Find Out How BIIB141 (Omaveloxolone) is Processed in the Body and to Learn More About Its Safety in Participants With Friedreich's Ataxia Aged 2 to 15 Years Old (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: Biogen | Trial completion date: Nov 2030 ➔ Jun 2030 | Trial primary completion date: Sep 2025 ➔ Jun 2030

Trial completion date • Trial primary completion date • Ataxia • Friedreich ataxia • Movement Disorders

Predicting disease progression in progressive cerebellar ataxias: integrating clinical, imaging, fluid, genetic, and digital biomarkers. (PubMed, Front Neurol) - "Disease-modifying therapies, notably antisense oligonucleotides and the approved compound omaveloxolone, are now entering or reaching the clinic, which makes reliable prediction of disease progression a central obstacle to trial success...Wearable-sensor gait and balance metrics detect change earlier than clinical scales and sharply reduce required sample sizes. We argue that no single modality satisfies every context of use, and that stage-specific, multimodal composites, integrated through harmonized international cohorts and machine learning, offer the most credible path to prognostic enrichment and to shorter, adequately powered, and preventive trials."

Biomarker • Journal • Review • Ataxia • CNS Disorders • Friedreich ataxia • Movement Disorders • NEFL

The HSE has given the go-ahead for the drug Skyclarys to be reimbursed after a long-running and emotionally charged campaign by people living with Friedreich’s ataxia who said it was their only hope of slowing the progressive illness (Irish Independent) - "The decision was made today at a meeting of senior HSE managers and follows a new price offer by the drug’s makers, Biogen....Before Biogen made its adjusted offer, the treatment had been estimated to cost around €280,000 per patient every year, with cost to the State estimated at around €130m over five years."

Reimbursement • Friedreich ataxia

Therapeutic potential of the Nrf2 activator omaveloxolone in spinocerebellar ataxia type 3 in cellular and Drosophila models. (PubMed, Front Pharmacol) - "Its effects were associated with activation of Nrf2-related antioxidant responses, p62 upregulation, and selected improvements in mitochondrial phenotypes. Further studies are needed to clarify the underlying mechanisms and determine the translational potential of RTA-408 for SCA3."

Journal • Ataxia • CNS Disorders • Friedreich ataxia • Metabolic Disorders • Movement Disorders • ATG7 • ATXN3 • BECN1 • LAMP2 • NQO1 • SOD2

Nfe2l2-knockout mouse model exhibits oxidative stress-associated stromal degeneration and inflammatory activation resembling keratoconus pathology. (PubMed, PeerJ) - "Importantly, pharmacological activation of NRF2 with the activator RTA-408 in complementary in vitro rescue experiments partially reversed oxidative stress and inflammation. These data support a feed-forward axis in which NRF2 deficiency drives oxidative stress, inflammation, and extracellular-matrix degradation that extends to corneal innervation, while NRF2 supplementation partially mitigates these pathological changes. The Nfe2l2-ko mouse exhibits several pathological features similar to those observed in human keratoconus and provides a platform to investigate disease mechanisms and evaluate NRF2-targeted interventions."

Journal • Preclinical • Inflammation • Ophthalmology • ALDH3A1 • CALCR • HMOX1 • ICAM1 • OCLN

Evolution of Friedreich's Ataxia Management Across Established and Emerging Therapies-Systematic Review and Meta-Analysis. (PubMed, J Clin Med) - "Omaveloxolone was the only agent showing a statistically significant improvement in mFARS (mean difference (MD) -2.40; 95% confidence interval (CI) -4.24 to -0.56; p = 0.014), supported by low-certainty evidence...No clear difference in overall adverse events was observed between intervention and control groups; however, available safety evidence remains limited by imprecision, small sample sizes, and short follow-up durations. Longer, standardized, and age-stratified randomized controlled trials (RCTs) are needed."

Journal • Retrospective data • Review • Ataxia • CNS Disorders • Friedreich ataxia • Metabolic Disorders • Movement Disorders

Omaveloxolone Driven NRF2 Activation as a Novel Therapeutic Strategy for Pulmonary Hypertension. (PubMed, Hypertension) - "Omaveloxolone attenuated PH, reduced right ventricular hypertrophy and vascular remodeling, and improved right ventricular function across hypoxia, monocrotaline, and sugen/hypoxia models under both preventive and therapeutic regimens. These findings demonstrate that Omaveloxolone exerts disease-modifying effects in PH by activating NRF2-dependent cytoprotective pathways, reducing oxidative stress, and suppressing inflammation, supporting its translational potential as a therapeutic strategy."

Journal • Ataxia • Cardiovascular • Congestive Heart Failure • Friedreich ataxia • Heart Failure • Hypertension • Inflammation • Movement Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • HIF1A • NFE2L2

Metal-dependent regulated cell death: Molecular architecture and translational frontiers. (PubMed, Imeta) - "To bridge the persistent knowledge gap between foundational metallobiology and clinical application, we evaluated a bidirectional therapeutic framework: exploiting synthetic lethality and metabolic gating via clinical inducers (e.g., sorafenib, elesclomol) to selectively eliminate therapy-resistant malignancies while deploying targeted pathway inhibitors and systemic agonists (e.g., dipyridamole, omaveloxolone) to limit pathological tissue degeneration in ischemic and neurodegenerative disorders. Specifically, we highlighted the integration of single-atom catalysts, stimuli-responsive nanomedicines, and biomimetic carriers engineered to spatiotemporally confine catalytic oxidative flux. Finally, we examined the systemic immunological consequences of targeted metal dysregulation, detailing how metal-induced immunogenic cell death and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway hyperactivation reshape immunosuppressive microenvironments..."

Journal • Review • CNS Disorders • Oncology • CGAS • STING

Omaveloxolone in Adult Friedreich Ataxia: A Real-World Cohort and Monitoring Approach (CNSF 2026) - "Multidimensional monitoring is feasible and essential to assess real-world safety and effectiveness of omaveloxolone in adult FA."

Clinical • Real-world • Real-world evidence • Ataxia • CNS Disorders • Movement Disorders

Long-Term Safety and Tolerability of Omaveloxolone in Patients With Friedreich Ataxia: Up to 6-Year Data From the MOXIe Open-Label Extension (CNSF 2026) - P2 | "This updated analysis provides up to 6 years of continuous long-term safety and tolerability data regarding omaveloxolone use in patients with FA. Safety findings were consistent with the previously known safety profile."

Clinical • Ataxia • CNS Disorders • Movement Disorders

Design and Outcome Measures of BRAVE, a Phase 3 Study of Omaveloxolone in Pediatric Patients With Friedreich Ataxia (CNSF 2026) - P3 | "Results will inform the efficacy and safety of omaveloxolone in patients with FA aged 2 to <16 years, aiming to expand approval for this pediatric population with unmet need."

Clinical • P3 data • Ataxia • CNS Disorders • Movement Disorders

Unlocking Sulforaphane's Potential in Friedreich Ataxia: Further Evidence from Preclinical Investigations Using Induced Pluripotent Stem Cell-Derived Sensory Neurons. (PubMed, Antioxid Redox Signal) - "Our preclinical data support SF as a strong FRDA drug candidate. Clinical evaluation is warranted to confirm its full therapeutic potential. Antioxid. Redox Signal. 00, 000-000."

Journal • Preclinical • Ataxia • CNS Disorders • Friedreich ataxia • Inflammation • Movement Disorders • FXN

Clinical experience with omaveloxolone in Friedreich’s ataxia in Portugal (OMAF-PT): Establishment of a prospective national registry (EAN 2026) - "This registry demonstrates the feasibility of nationwide, prospective real-world monitoring of omaveloxolone in FA. While early access enabled treatment initiation in over half of eligible patients, a substantial proportion remained untreated. Continued follow-up will be essential to evaluate long-term safety and clinical outcomes as treatment availability expands."

Clinical • Ataxia • Friedreich ataxia • Movement Disorders

Omaveloxolone for Friedreich ataxia: What does 'Cochrane' have to say about it? (EAN 2026) - " Pharmacological treatments probably make little or no difference to change in ataxia rating scale (ARS) but improved upper limb dexterity (ULD) There was variation in that omaveloxolone helped ARS and leriglitazone helped ULD. The seven RCTs' outcomes were downgraded due to imprecision to small number of participants or wide confidence intervals. This would suggest that studies with approximately 200 or more events are required to help capture the subtle changes that occur over time in this slowly progressive disease."

Ataxia • Cardiomyopathy • Cardiovascular • Diabetes • Friedreich ataxia • Metabolic Disorders • Movement Disorders

Longitudinal experience with Omaveloxolone in Friedreich’s ataxia: insights from the french cohort at CHU Bordeaux (EAN 2026) - "After 12 months, the mean change in SARA score from baseline was −0.02 SD 2.74, indicating overall stability. This finding is consistent with a slowing of disease progression and contrasts with natural history data from the EFACTS cohort, where ambulant patients show an average annual SARA increase of +0.82 SD 0.05, suggesting a potential attenuation of disease progression"

Ataxia • Friedreich ataxia • Metabolic Disorders • Movement Disorders • FXN

A Study to Learn How BIIB141 (Omaveloxolone) Affects the Health of Participants With Friedrich's Ataxia Who Took it During Pregnancy and/or During Breastfeeding and About the Health of Their Babies (clinicaltrials.gov) - P=N/A | N=10 | Recruiting | Sponsor: Biogen | N=20 ➔ 10

Adverse events • Enrollment change • Ataxia • Friedreich ataxia • Movement Disorders

Key Interventions in Friedreich's Ataxia and Their Impact on Patient Outcomes: A Systematic Review. (PubMed, Mov Disord) - "Pharmacological interventions (66.7%), mainly disease modifying (93.5%), were more common than nonpharmacological interventions, with the most effective interventions being omaveloxolone (pharmacological), as well as rehabilitation and heart interventions (nonpharmacological).."

Journal • Review • Ataxia • CNS Disorders • Friedreich ataxia • Movement Disorders • Parkinson's Disease

RTA-408 Enhances Nrf2 Activation and Mitochondrial Function to Improve SCA3 Cell and Drosophila Models (EAN 2026) - "RTA-408 confers neuroprotection in SCA3 models by activating Nrf2 signaling and improving mitochondrial function. The reduction of mutant ataxin-3 likely reflects decreased protein accumulation or enhanced clearance secondary to improved cellular redox homeostasis, supporting Nrf2-targeted mitochondrial modulation as a potential disease-modifying strategy for SCA3."

Ataxia • Friedreich ataxia • Metabolic Disorders • Movement Disorders • Neuroblastoma • Ophthalmology • Solid Tumor • ATXN3

Multitarget therapeutic potential of sulforaphane in ethidium bromide-induced neurotoxicity in multiple sclerosis-like pathology: comparison with omaveloxolone and dimethyl fumarate on neuroprotection and systemic recovery. (PubMed, Sci Rep) - "These findings suggest that SFN3 may have therapeutic potential for further translational research in MS. Future studies should validate its clinical relevance and explore combinatorial therapies with existing MS treatments to enhance therapeutic outcomes."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • MAPT • STAT3

A single-center experience with Omaveloxolone in Friedreich Ataxia (EAN 2026) - "Omaveloxolone was safe and well tolerated, with mFARS and FA-ADL improvements more evident in patients with advanced disease and higher baseline scores."

Clinical • Ataxia • Friedreich ataxia • Metabolic Disorders • Movement Disorders • FXN

Impact of Omaveloxolone on Serum Lipids in Patients with Friedreich Ataxia: A 1-Year Real-World Analysis. (PubMed, CNS Drugs) - "In this real-world Friedreich ataxia cohort, omaveloxolone treatment was associated with a sustained shift toward a more atherogenic lipid profile, driven almost entirely by increased low-density lipoprotein-cholesterol and ApoB levels. This pattern is consistent with impaired hepatic clearance of ApoB-containing particles rather than increased production, supporting routine lipid monitoring and further evaluation of long-term cardiovascular risk."

Journal • Real-world evidence • Ataxia • Cardiovascular • CNS Disorders • Dyslipidemia • Friedreich ataxia • Metabolic Disorders • Movement Disorders • APOA1 • APOB • CRP

RTA-408 induces JNK-dependent apoptosis and autophagy in breast cancer cells. (PubMed, Oncol Lett) - "Cell viability was quantified using a tetrazolium-based colorimetric assay and apoptosis was evaluated by the Muse® Annexin V & Dead Cell assay based on Annexin V and 7-amino-actinomycin D staining; the expression levels of JNK, p38, ERK, beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), p62/sequestosome 1 (SQSTM1) and poly (ADP-ribose) polymerase (PARP) were assessed by western blotting. Pharmacological inhibition with SP600125 attenuated JNK phosphorylation, reduced apoptotic responses and diminished autophagy-associated marker accumulation, supporting the notion that JNK signaling contributes, at least in part, to these effects. These findings indicate that RTA-408 exerts nanomolar antiproliferative activity in both hormone receptor-positive and triple-negative BC cells through a JNK-dependent mechanism that simultaneously engages apoptosis and autophagy, supporting further in vivo and translational investigation."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • BECN1 • ER • MAP1LC3B • SQSTM1

Pharmacological Activation of NRF2 by Omaveloxolone Upregulates NRF2-Target Proteins in SMA Type I Human Fibroblasts. (PubMed, FASEB J) - "Together, these findings support diminished NRF2 pathway activity as a feature of SMA fibroblasts and demonstrate that OMAV activates NRF2 signaling in this human SMA cellular model, consistent with enhanced cytoprotective signaling. These results support further investigation of NRF2 activation, including OMAV, as a potential adjunctive strategy in SMA."

Journal • Ataxia • Friedreich ataxia • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • NQO1 • SLC7A11