Skyclarys (omaveloxolone) / Biogen - LARVOL DELTA

omaveloxolone (Skyclarys) is not recommended for use within NHSScotland (Scottish Medicines Consortium) - "Indication under review: for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older. In a randomised, double-blind, phase II study, omaveloxolone improved the modified Friedreich’s ataxia rating scale (mFARS) score from baseline to week 48 compared with placebo; this was statistically significant and clinically relevant. The submitting company’s justification of the treatment’s cost in relation to its health benefits was not sufficient and in addition the company did not present a sufficiently robust economic analysis to gain acceptance by SMC."

Reimbursement • Friedreich ataxia

Targeting the Keap1-Nrf2 Axis in COPD: Comparative analysis of electrophilic and peptide-based Nrf2 activators in airway and immune cells. (PubMed, Eur J Pharmacol) - "These results confirm that the Nrf2 pathway is compromised in COPD and support selective Nrf2 activation-particularly via peptide-based approaches-as a promising therapeutic strategy to mitigate oxidative and inflammatory injury in the disease."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL6 • KEAP1 • MMP9 • NFE2L2 • NQO1

Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma. (PubMed, Cell Death Dis) - "Notably, ERAD inhibition by RTA408 is cytotoxic to primary malignant plasma cells, including those resistant to proteasome inhibitors, and demonstrates in vivo anti-myeloma activity. Our findings establish a novel ERAD inhibitor, which is a valuable tool to dissect ERAD biology, and provide pre-clinical evidence for RTA408 as a therapeutic agent in MM."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • CASP8

RWE FOR SINGLE AND WELL-CONTROLLED STUDIES: AN EVALUATION OF FDA SUBMISSIONS FOR EFFECTIVENESS (ISPOR 2026) - "Examples of medicines where regulators categorized RWE as a single well-controlled study included palovarotene and tacrolimus while RWE as confirmatory included omaveloxolone, alpelisib, and pneumococcal 20-valent conjugate vaccine. While RWE use in MAAs has increased substantially, regulatory acceptability of RWE—particularly for effectiveness—has varied based on totality of evidence. Sponsors should consider the totality of evidence when incorporating RWE into MAAs."

Hematological Disorders • Infectious Disease • Pneumococcal Infections • Rare Diseases

A Single-center Experience with Omaveloxolone in Friedreich Ataxia (AAN 2026) - "Omaveloxolone was safe and well tolerated. mFARS and FA-ADL showed a higher improvement in patients with a more advanced disease and higher baseline scores at both scales."

Clinical • Ataxia • CNS Disorders • Dental Disorders • Friedreich ataxia • Metabolic Disorders • Movement Disorders • Stomatitis

Early Experience on Omaveloxolone in Adult Patients with Friedreich's Ataxia: A Real-world Observational Study (AAN 2026) - "Omav seems to be safe and well-tolerated in adult FRDA patients in the real-life setting. Stabilization of neurological symptoms are very promising, as well as the improvement of inflammatory biomarkers, but no predictive factors for the disease response have been identified. However, the short duration, and the small sample size limit the generalizability of the results."

Clinical • Observational data • Real-world • Real-world evidence • Ataxia • Cardiovascular • CNS Disorders • Congestive Heart Failure • Friedreich ataxia • Heart Failure • Movement Disorders • Musculoskeletal Diseases • Renal Disease • IL6

A New Method for the Treatment of Premature Ovarian Insufficiency Based on the Effect of Omaveloxolone (RTA 408) on the Mitochondrial Function of Granulosa Cells (ISGE 2026) - "Mitochondrial dysfunction was induced by exposure to cyclophosphamide (0.1 mg/mL, 6 hours). Keywords. premature ovarian insufficiency; omaveloxolone; RTA 408; granulosa cells"

Endocrine Disorders • Infertility • Metabolic Disorders • Sexual Disorders • Women's Health

Treatment with omaveloxolone in Friedreich's ataxia: one-year real-world efficacy and safety data. (HMGC 2026) - "The dynamism of the BRAIN-TEAM and FILNEMUS networks enabled the efficient inclusion of patients in this first early access program for Friedreich's ataxia. This study will provide more precise data on French patients treated with Omaveloxolone, real-world efficacy and safety data for this population, and thus guide clinicians in their use of this molecule."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Ataxia • Friedreich ataxia • Movement Disorders • Rare Diseases

Biogen reports strong fourth quarter and full year 2025 results and provides full year 2026 financial guidance (Biogen Press Release) - "LEQEMBI fourth quarter global in-market sales of approximately $134 million, up 54% year-over-year, with U.S. in-market sales of approximately $78 million, representing continued growth; SKYCLARYS grew global patients on therapy by approximately 30% in 2025; fourth quarter U.S. revenue of approximately $89 million driven by demand growth, with ex-U.S. revenue of approximately $44 million reflecting continued demand growth, also impacted by a one-time reimbursement true-up; ZURZUVAE fourth quarter revenue of approximately $66 million showed strong continued demand growth; VUMERITY grew 3% year-over-year in the fourth quarter; SPINRAZA fourth quarter revenue declined 15% year-over-year, impacted by timing of shipments outside the U.S., with full year revenue down 2% year-over-year."

Commercial • Alzheimer's Disease • Depression • Friedreich ataxia • Multiple Sclerosis • Muscular Atrophy • Ocular Inflammation • Pain • Parkinson's Disease

Sulforaphane-Mediated Multitarget Therapeutic Effects in Methylmercury-Induced ALS-Like Pathology: Comparative Analysis and Multifaceted Approach to Neuroprotection and Systemic Recovery. (PubMed, Mol Neurobiol) - "The objective of this study was to evaluate the neuroprotective efficacy and safety of sulforaphane (SUFP) in a methylmercury (MMHg⁺)-induced preclinical rat model of ALS, with comparison to omaveloxolone (OVX) and dimethyl fumarate (DIMT)...Molecular docking further supported SUFP's interaction with Nrf2-Keap1 targets, reinforcing its antioxidant and anti-inflammatory mechanisms. Collectively, these findings identify SUFP as a multifaceted and well-tolerated therapeutic candidate for ALS, supporting its further translational and clinical evaluation."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Hematological Disorders • Inflammation • BAX • CASP3 • IL1B • KEAP1 • NGFR • SIRT1 • TNFA

Omaveloxolone promotes functional recovery of spinal cord injury by reducing inflammatory response and regulating macrophage polarization. (PubMed, Front Mol Neurosci) - "Our results collectively confirm the efficacy of Omav in repairing spinal cord injury by targeting macrophage polarization and regulating inflammatory responses. This study not only highlights the therapeutic potential of Omav for SCI but also provides a novel pharmacological strategy for SCI treatment."

Journal • CNS Disorders • Inflammation • Orthopedics

Targeting frataxin deficiency in DRG neurons and fibroblasts: omaveloxolone restores metabolic and iron balance to reduce ferroptosis. (PubMed, Biomed Pharmacother) - "This combination enhanced cell survival and produced a synergistic effect increasing mitochondrial respiration in frataxin-deficient DRG neurons. In summary, these findings demonstrate the beneficial effects of omaveloxolone and further suggest that combination therapy with honokiol may provide an effective strategy for the treatment of FA, potentially mitigating adverse effects."

Journal • Ataxia • CNS Disorders • Friedreich ataxia • Movement Disorders • GPX4 • SIRT3

A Study to Learn About the Effects and Safety of RTA 408 (Omaveloxolone) in People Aged 16 to 40 With Friedreich's Ataxia (clinicaltrials.gov) - P2 | N=172 | Completed | Sponsor: Biogen | Active, not recruiting ➔ Completed

Trial completion • Ataxia • Friedreich ataxia • Movement Disorders

Pharmacotherapy of neuromuscular diseases : what's new in 2025 (PubMed, Rev Med Suisse) - "Two new drugs have recently become available for treating neuromuscular diseases: omaveloxolone and tofersen. Tofersen is an antisense oligonucleotide that induces posttranscriptional silencing of the SOD1 (superoxide dismutase 1) gene, which is involved in familial forms of amyotrophic lateral sclerosis. Although its efficacy has so far only been indirectly demonstrated through its ability to reduce serum neurofilament levels, it is available on a compassionate use basis in Switzerland."

Journal • Amyotrophic Lateral Sclerosis • Ataxia • CNS Disorders • Friedreich ataxia • Movement Disorders • SOD1

A Study to Learn How the Body Processes BIIB141 (Omaveloxolone) When Taken as a Capsule or as a Tablet Dissolved in Liquid, and to Learn About Its Safety in Healthy Adults Ages 18 to 55 (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open

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=35 | Recruiting | Sponsor: Biogen | Trial completion date: Feb 2030 ➔ Nov 2030

Trial completion date • Ataxia • Friedreich ataxia • Movement Disorders

Patient-reported, psychosocial and health economic outcomes in mild to moderate Friedreich's ataxia: baseline results of the PROFA study. (PubMed, Lancet Reg Health Eur) - "Omaveloxolone was used by 33 patients (32.7%)...The results emphasize the multidimensional patient, societal, and economic burden of FA and the need for comprehensive care addressing physical, mental, and psychosocial health. European Joint Programme on Rare Diseases (EJP RD)."

HEOR • Journal • Ataxia • Developmental Disorders • Friedreich ataxia • Movement Disorders • Rare Diseases

Transcriptomic profiling of human endothelial cells infected with venezuelan equine encephalitis virus reveals NRF2 driven host reprogramming mediated by omaveloxolone treatment. (PubMed, Front Genet) - "Network analyses highlighted NRF2-driven antioxidant modules under OMA and cytokine-chemokine modules under untreated infection. These findings demonstrate that OMA redirects host transcription from an interferon-centric, inflammatory response toward an NRF2-driven cytoprotective program while preserving core antiviral mechanisms, which supports NRF2 activation as a therapeutic strategy against VEEV."

Journal • CNS Disorders • Infectious Disease • Inflammation • CXCL10 • CXCL11 • HMOX1 • IFIT1 • IL6 • MX1 • NQO1 • OASL • RSAD2 • SLC7A11

Synthetic Oleanane Triterpenoids Reduce Tumor Growth and Promote an Anti-Tumor Immune Response Independent of Cancer KEAP1 Mutational Status. (PubMed, Antioxidants (Basel)) - "Similarly, subcutaneous KEAP1 KO tumors were larger and more immune-suppressed compared to WT tumors. Both CDDO-Me and omaveloxolone reduced the tumor burden and improved immune cell phenotypes within the TIME independent of KEAP1 mutational status."

Journal • Lung Cancer • Oncology • Solid Tumor • KEAP1

Ferroptosis-associated transcriptional factors in neurological diseases: molecular mechanisms and therapeutic prospects. (PubMed, Exp Mol Med) - "The fact that Nrf2 activator RTA-408 is approved for clinical evaluation (phase 2 clinical trial) of its efficacy and safety in patients with Alzheimer's disease supports this notion. Future research on proteolysis-targeting chimera (PROTAC) and gene therapy holds promise for optimization of neurological disease treatment."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Epilepsy • Gene Therapies • Movement Disorders • Orthopedics • Parkinson's Disease • Targeted Protein Degradation • Vascular Neurology

The Role of Natural Product Chemistry in Drug Discovery: Two Decades of Progress and Perspectives. (PubMed, J Nat Prod) - "Six NP-D case studies illustrating successful progression from discovery to clinical use were highlighted: omaveloxolone (novel pharmacology, first-in-class), fidaxomicin, ibrexafungerp, epoxomicin, eribulin (known pharmacology, new drug class), and the gliflozin drug family (13 members)...Although overall NP-D drug sales have declined, dapagliflozin and empagliflozin demonstrate that blockbuster status is still achievable. While growth is modest, NPs remain highly valuable active pharmaceutical ingredients (APIs) with substantial clinical impact. Significant opportunities persist for drug-focused NP R&D efforts, as many recently validated therapeutic targets remain underexplored for NP-D chemotypes."

Journal • Review

Ferroptosis is a novel pathogenic mechanism of FDXR-related disease via disruption of the NRF2 pathway. (PubMed, Cell Death Discov) - "Finally, administration of the NRF2 activator omaveloxolone, which was recently approved by the FDA for treatment of Friedreich's ataxia, helps mitigate the pathogenesis. Together, our results suggest that ferroptosis is a novel underlying mechanism of FDXR-related disease and that activation of NRF2 could be an immediate, viable treatment option for individuals with FDXR-related disease and other conditions involving aberrant iron metabolism."

Journal • Ataxia • Friedreich ataxia • Metabolic Disorders • Movement Disorders • FDXR • SLC7A11

A Study to Learn How the Body Processes BIIB141 (Omaveloxolone) When Taken as a Capsule or as a Tablet Dissolved in Liquid, and to Learn About Its Safety in Healthy Adults Ages 18 to 55 (clinicaltrials.gov) - P1 | N=70 | Not yet recruiting | Sponsor: Biogen

New P1 trial

The role of glutamine/Nrf2-enhanced PHGDH in Cadmium-induced lactate utilization. (PubMed, Free Radic Biol Med) - "Moreover, inhibition of Nrf2 with ML385 attenuated Cd-induced glutamine metabolism, PHGDH, MCT1, lactate production, and cell migration, while activation of Nrf2 with RTA-408 had the opposite effect...Collectively, these findings suggest that PHGDH plays a crucial role in Cd-induced lactate utilization, and the mechanism underlies the interaction between glutamine and Nrf2. This study provides insights into the mechanism of Cd-related tumorigenesis and toxicity."

Journal • Lung Cancer • Oncology • Solid Tumor • PHGDH • SLC16A1

Treatment of primary adult-onset neurodegenerative cerebellar ataxias. (PubMed, Neurotherapeutics) - "Pharmacological approaches, including omaveloxolone for Friedreich's ataxia and off-label agents such as riluzole, 4-aminopyridine, and varenicline, demonstrate subtype-specific benefits. In parallel, molecular and gene-based therapies-including antisense oligonucleotides, viral vector delivery systems, and CRISPR-based strategies-are advancing into preclinical and early-phase clinical studies. This evolving therapeutic landscape underscores a shift toward personalized, multimodal care for cerebellar ataxias and highlights the need for continued translational efforts to bridge mechanistic insights with clinical impact."

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