Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations
Abstract Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years and is under clinical development for pediatric patients. In the MOXIe study, alanine and aspartate aminotransferase (ALT and AST) elevations were among the most common treatment-emergent adver...
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Adis, Springer Healthcare
2025-06-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-025-00752-8 |
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| author | Susan Perlman Mathieu Anheim Sylvia Boesch James H. Lewis David R. Lynch |
| author_facet | Susan Perlman Mathieu Anheim Sylvia Boesch James H. Lewis David R. Lynch |
| author_sort | Susan Perlman |
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| description | Abstract Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years and is under clinical development for pediatric patients. In the MOXIe study, alanine and aspartate aminotransferase (ALT and AST) elevations were among the most common treatment-emergent adverse events (TEAEs) in the omaveloxolone arm and were mild to moderate, generally asymptomatic, transient, and reversible; no patients who received omaveloxolone had laboratory abnormalities that met the Hy’s law criteria. Omaveloxolone labels (US and EU) provide guidance for monitoring and managing these elevations. Here, practical use considerations, from experience-based opinions of four FA experts and a hepatologist via semi-structured interviews, are presented. Prior to omaveloxolone initiation, assessment of baseline ALT, AST, and total bilirubin is recommended per label. During treatment, ALT, AST, and total bilirubin should be monitored monthly for the first 3 months and periodically thereafter per label. Reduced frequency of patient monitoring after 3 months is suggested if aminotransferase levels remain normal. Per label, omaveloxolone should be temporarily discontinued if aminotransferases increase to > 5 × the upper limit of normal (ULN) or > 3 × ULN with other evidence of liver dysfunction. Stemming from real-world practical considerations wherein patients are followed up less frequently than in the trial setting, treatment interruption when aminotransferases increase to ≥ 3 × ULN without other signs of hepatic impairment may be considered. When aminotransferase elevations stabilize or resolve, omaveloxolone may be reinitiated with an appropriate increased frequency of monitoring of liver function per label. We propose patients who pause treatment may have testing repeated after 2 weeks, while those with resolving aminotransferase elevations may reinitiate omaveloxolone with stepwise dose titrations and testing every 2 weeks for ≈ 3 months. Use considerations herein may inform decisions on monitoring and managing ALT and AST elevations, which potentially help to encourage the treatment adherence needed to achieve the slowing of FA progression seen in MOXIe. Graphical abstract available for this article. Graphical Abstract |
| format | Article |
| id | doaj-art-9f0061821e204f76962f12e91aae8fbd |
| institution | Kabale University |
| issn | 2193-8253 2193-6536 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Neurology and Therapy |
| spelling | doaj-art-9f0061821e204f76962f12e91aae8fbd2025-08-20T04:03:07ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362025-06-011441209122710.1007/s40120-025-00752-8Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use ConsiderationsSusan Perlman0Mathieu Anheim1Sylvia Boesch2James H. Lewis3David R. Lynch4Department of Neurology, David Geffen School of Medicine, University of California Los AngelesDepartment of Neurology, University Hospital of StrasbourgCenter for Rare Movement Disorders Innsbruck, Department of Neurology, Medical University of InnsbruckDepartment of Medicine, Division of Gastroenterology-Hepatology, MedStar Georgetown University HospitalDivision of Neurology and Pediatrics, Children’s Hospital of Philadelphia, Abramson Research CenterAbstract Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years and is under clinical development for pediatric patients. In the MOXIe study, alanine and aspartate aminotransferase (ALT and AST) elevations were among the most common treatment-emergent adverse events (TEAEs) in the omaveloxolone arm and were mild to moderate, generally asymptomatic, transient, and reversible; no patients who received omaveloxolone had laboratory abnormalities that met the Hy’s law criteria. Omaveloxolone labels (US and EU) provide guidance for monitoring and managing these elevations. Here, practical use considerations, from experience-based opinions of four FA experts and a hepatologist via semi-structured interviews, are presented. Prior to omaveloxolone initiation, assessment of baseline ALT, AST, and total bilirubin is recommended per label. During treatment, ALT, AST, and total bilirubin should be monitored monthly for the first 3 months and periodically thereafter per label. Reduced frequency of patient monitoring after 3 months is suggested if aminotransferase levels remain normal. Per label, omaveloxolone should be temporarily discontinued if aminotransferases increase to > 5 × the upper limit of normal (ULN) or > 3 × ULN with other evidence of liver dysfunction. Stemming from real-world practical considerations wherein patients are followed up less frequently than in the trial setting, treatment interruption when aminotransferases increase to ≥ 3 × ULN without other signs of hepatic impairment may be considered. When aminotransferase elevations stabilize or resolve, omaveloxolone may be reinitiated with an appropriate increased frequency of monitoring of liver function per label. We propose patients who pause treatment may have testing repeated after 2 weeks, while those with resolving aminotransferase elevations may reinitiate omaveloxolone with stepwise dose titrations and testing every 2 weeks for ≈ 3 months. Use considerations herein may inform decisions on monitoring and managing ALT and AST elevations, which potentially help to encourage the treatment adherence needed to achieve the slowing of FA progression seen in MOXIe. Graphical abstract available for this article. Graphical Abstracthttps://doi.org/10.1007/s40120-025-00752-8Alanine aminotransferase (ALT)Aspartate aminotransferase (AST)Drug-induced liver injury (DILI)Friedreich ataxiaLiver function testNuclear factor-erythroid 2-related factor 2 (Nrf2) |
| spellingShingle | Susan Perlman Mathieu Anheim Sylvia Boesch James H. Lewis David R. Lynch Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations Neurology and Therapy Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Drug-induced liver injury (DILI) Friedreich ataxia Liver function test Nuclear factor-erythroid 2-related factor 2 (Nrf2) |
| title | Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations |
| title_full | Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations |
| title_fullStr | Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations |
| title_full_unstemmed | Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations |
| title_short | Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations |
| title_sort | managing aminotransferase elevations in patients with friedreich ataxia treated with omaveloxolone a review and expert opinion on use considerations |
| topic | Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Drug-induced liver injury (DILI) Friedreich ataxia Liver function test Nuclear factor-erythroid 2-related factor 2 (Nrf2) |
| url | https://doi.org/10.1007/s40120-025-00752-8 |
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