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weeks. Of the research participants, 53% were male, 97% were white, and the mean age was 24 years at study entry. Nine (18%) patients were younger than age 18. The primary objective was to evaluate the change in the modified
Friedreich's Ataxia Rating Scale (mFARS) score compared to placebo at week 48. The mFARS is a clinical assessment that measures disease progression, namely swallowing and speech (bulbar), upper limb coordination, lower limb coordination, and upright stability. Individuals receiving omaveloxolone performed better on the mFARS than people receiving placebo.
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Friedreich's ataxia causes progressive damage to the spinal cord, peripheral nerves, and the brain, resulting in uncoordinated muscle movement, poor balance, difficulty walking, changes in speech and swallowing, and a shortened lifespan. The condition can also cause heart disease. This disease tends
764:
adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product
Skyclarys, intended for the treatment of Friedreich's ataxia. The applicant for this medicinal product is Reata Ireland Limited. Omaveloxolone was approved for medical use in the European
720:
The efficacy and safety of omaveloxolone was evaluated in a 48-week randomized, placebo-controlled, and double-blind study and an open-label extension. Study 1 enrolled 103 individuals with
Friedreich's ataxia who received placebo (52 individuals) or omaveloxolone 150 mg (51 individuals) for 48
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The most common side effects include an increase in alanine transaminase and an increase of aspartate aminotransferase, which can be signs of liver damage, headache, nausea, abdominal pain, fatigue, diarrhea and musculoskeletal pain.
657:), which provide a specific and finite antioxidative potential, omaveloxolone, through Nrf2, broadly activates intracellular and mitochondrial antioxidative pathways, in addition to pathways that may directly increase
521:
InChI=1S/C32H43NO4/c1-27(2)11-13-32(26(36)37-8)14-12-31(7)24(20(32)17-27)21(34)15-23-29(5)16-19(18-33)25(35)28(3,4)22(29)9-10-30(23,31)6/h15-16,20,22,24H,9-14,17H2,1-8H3/t20-,22-,24-,29-,30+,31+,32-/m0/s1
205:
N-((4aS,6aR,6bS,8aR,12aS,14aR,14bS)-1 1-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b- octadecahydropicen-4a-yl)-2,2-difluoropropanamide
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Reisman SA, Lee CY, Meyer CJ, Proksch JW, Ward KW (July 2014). "Topical application of the synthetic triterpenoid RTA 408 activates Nrf2 and induces cytoprotective genes in rat skin".
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The mechanism of action of omaveloxolone and its related compounds has been demonstrated to be through a combination of activation of the antioxidative transcription factor
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transcriptionally regulates multiple genes that play both direct and indirect roles in producing antioxidative potential and the production of cellular energy (
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970:"Reata Pharmaceuticals Announces FDA Approval of Skyclarys (Omavaloxolone), the First and Only Drug Indicated for Patients with Friedreich's Ataxia"
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Although rare, Friedreich's ataxia is the most common form of hereditary ataxia in the United States, affecting about one in every 50,000 people.
1192:"Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis"
853:
Text was copied from this source which is copyright
European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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Omaveloxolone was approved for medical use in the United States in
February 2023, and in the European Union in February 2024. The US
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Subramony SH, Lynch DL (May 2023). "A Milestone in the
Treatment of Ataxias: Approval of Omaveloxolone for Friedreich Ataxia".
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Omaveloxolone is a second generation member of the synthetic oleanane triterpenoid compounds and in clinical development by
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1241:"Topical application of the synthetic triterpenoid RTA 408 protects mice from radiation-induced dermatitis"
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Neymotin A, Calingasan NY, Wille E, Naseri N, Petri S, Damiano M, et al. (July 2011).
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697:. Omaveloxolone is under clinical investigation for a variety of indications, including
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Omaveloxolone was approved for medical use in the United States in
February 2023.
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O=C4C(\C#N)=C/5(/C3=C/C(=O)2(CC1(NC(=O)C(F)(F)C)CCC(C)(C)C12)(C)3(C)CC5C4(C)C)C
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Reisman SA, Lee CY, Meyer CJ, Proksch JW, Sonis ST, Ward KW (May 2014).
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for "RTA 408 Capsules in
Patients With Friedreich's Ataxia - MOXIe" at
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to develop in children and teenagers and gradually worsens over time.
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This article incorporates text from this source, which is in the
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and inhibition of the pro-inflammatory transcription factor
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728:(FDA) granted the application for omaveloxolone
641:. Consequently, unlike exogenously administered
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685:have demonstrated that omaveloxolone possesses
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758:Committee for Medicinal Products for Human Use
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740:, and rare pediatric disease designations.
600:for the treatment of Friedreich's ataxia.
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843:from the original on 15 December 2023
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871:Union Register of medicinal products
1208:10.1016/j.freeradbiomed.2011.03.027
1196:Free Radical Biology & Medicine
1146:Archives of Dermatological Research
976:(Press release). 28 February 2023.
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794:"Skyclarys- omaveloxolone capsule"
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980:from the original on 1 March 2023
940:from the original on 1 March 2023
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804:from the original on 1 July 2023
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1105:New Drug Therapy Approvals 2023
1001:"Omaveloxolone: First Approval"
867:"Skyclarys product information"
526:Key:WPTTVJLTNAWYAO-KPOXMGGZSA-N
1344:Drugs not assigned an ATC code
445:
421:
1:
1114:Food and Drug Administration
932:Food and Drug Administration
726:Food and Drug Administration
633:, adenosine triphosphate or
582:Food and Drug Administration
557:, sold under the brand name
695:mitochondrial bioenergetics
584:(FDA) considers it to be a
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1072:10.1007/s12311-023-01568-8
1017:10.1007/s40265-023-01874-9
974:Reata Pharmaceuticals Inc.
565:used for the treatment of
411:Chemical and physical data
1158:10.1007/s00403-013-1433-7
839:(EMA). 14 December 2023.
837:European Medicines Agency
762:European Medicines Agency
586:first-in-class medication
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1118:(Report). January 2024.
765:Union in February 2024.
711:corneal endothelial cell
703:mitochondrial myopathies
659:mitochondrial biogenesis
1299:Clinical trial number
756:In December 2023, the
679:Reata Pharmaceuticals
936:. 28 February 2023.
709:, and prevention of
1257:2014RadR..181..512R
999:Lee A (June 2023).
744:Society and culture
699:Friedreich's ataxia
683:Preclinical studies
611:Mechanism of action
567:Friedreich's ataxia
36:
1307:ClinicalTrials.gov
1245:Radiation Research
873:. 12 February 2024
1266:10.1667/RR13578.1
691:anti-inflammatory
596:Omaveloxolone is
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1202:(1): 88–96.
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806:. Retrieved
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749:Legal status
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655:Coenzyme Q10
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643:antioxidants
639:mitochondria
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369:CHEBI:229661
224:1474034-05-3
156:Legal status
150:Legal status
91:License data
29:
1364:Triterpenes
1302:NCT02255435
1043:16 December
984:28 February
944:28 February
877:19 February
847:16 December
808:16 December
730:orphan drug
463: g·mol
189:Identifiers
64:Other names
55:Trade names
1338:Categories
1060:Cerebellum
769:References
734:fast track
563:medication
468:3D model (
456:Molar mass
329:G69Z98951Q
300:ChemSpider
260:IUPHAR/BPS
215:CAS Number
198:IUPAC name
27:Medication
1126:9 January
1088:258843532
1033:258567442
661:(such as
651:vitamin E
598:indicated
559:Skyclarys
121:Routes of
83:Monograph
77:Drugs.com
59:Skyclarys
18:Skyclarys
1359:Steroids
1328:Medicine
1283:23906747
1275:24720753
1226:21457778
1174:25733020
1166:24362512
1120:Archived
1080:37219716
1037:Archived
1025:37155124
978:Archived
938:Archived
841:Archived
802:Archived
798:DailyMed
571:by mouth
545:(verify)
309:34980948
280:DrugBank
249:71811910
135:ATC code
128:By mouth
105:DailyMed
1253:Bibcode
1217:3109235
724:The US
673:History
561:, is a
461:554.723
417:Formula
289:DB12513
235:PubChem
107::
67:RTA 408
1314:Portal
1281:
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1214:
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1164:
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1078:
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1023:
665:) and
494:SMILES
349:D10964
171:℞-only
169:
103:
1279:S2CID
1170:S2CID
1116:(FDA)
1112:U.S.
1108:(PDF)
1084:S2CID
1029:S2CID
1005:Drugs
934:(FDA)
930:U.S.
663:PGC1α
621:NF-κB
514:InChI
470:JSmol
360:ChEBI
1271:PMID
1222:PMID
1162:PMID
1128:2024
1076:PMID
1045:2023
1021:PMID
986:2023
946:2023
879:2024
849:2023
810:2023
689:and
647:e.g.
631:i.e.
627:Nrf2
617:Nrf2
340:KEGG
320:UNII
269:7573
142:None
73:AHFS
1261:doi
1249:181
1212:PMC
1204:doi
1154:doi
1150:306
1068:doi
1013:doi
653:or
635:ATP
385:EPA
239:CID
1340::
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887:^
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573:.
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425:33
177:EU
165:US
100:US
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