Enasidenib

Enasidenib
Names
Trade namesIdhifa
Other namesEnasidenib mesylate, AG-221
Clinical data
Drug classIsocitrate dehydrogenase 2 inhibitor[1]
Main usesAcute myeloid leukemia (AML)[1]
Side effectsNausea, diarrhea, high bilirubin, lose of appetite[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
  • US: N (Not classified yet)
    Routes of
    use    		By mouth
    Typical dose100mg OD[2]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa617040
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only
    Chemical and physical data
    FormulaC19H17F6N7O
    Molar mass473.383 g·mol−1
    3D model (JSmol)
    SMILES
    • CC(C)(CNC1=NC(=NC(=N1)NC2=CC(=NC=C2)C(F)(F)F)C3=NC(=CC=C3)C(F)(F)F)O
    InChI
    • InChI=InChI=1S/C19H17F6N7O/c1-17(2,33)9-27-15-30-14(11-4-3-5-12(29-11)18(20,21)22)31-16(32-15)28-10-6-7-26-13(8-10)19(23,24)25/h3-8,33H,9H2,1-2H3,(H2,26,27,28,30,31,32)
    • Key:DYLUUSLLRIQKOE-UHFFFAOYSA-N

    Enasidenib, sold under the brand name Idhifa, is a medication used to treat acute myeloid leukemia (AML) with mutations of the isocitrate dehydrogenase 2 (IDH2) gene.[1] It is used when other treatments have failed.[2] It is taken by mouth.[2]

    Common side effects include nausea, diarrhea, high bilirubin, and lose of appetite.[2] Other side effects may include differentiation syndrome, tumor lysis syndrome, lung problems, infertility, and kidney problems.[1] Use during pregnancy may harm the baby.[2] It works by blocking the action of mutated IDH2.[3]

    Enasidenib was approved for medical use in the United States in 2017.[1] It was denied approval in Europe in 2019 due to insufficient evidence of benefit.[3] In the United States a month of treatment costs about 29,500 USD as of 2021.[4]

    Medical use

    Enasidenib is used to treat relapsed or refractory acute myeloid leukemia in people with specific mutations of the IDH2 gene, determined by an FDA-approved IDH2 companion diagnostic test.[5]

    Dosage

    It is taken at a dose of 100 mg per day.[2]

    Side effects

    The main serious adverse effect of enasidenib is differentiation syndrome.[6]

    Pharmacology

    Isocitrate dehydrogenase is a critical enzyme in the citric acid cycle. Mutated forms of IDH produce high levels of the (R)-enantiomer of 2-hydroxyglutarate (R-2-HG) and can contribute to the growth of tumors. IDH1 catalyzes this reaction in the cytoplasm, while IDH2 catalyzes this reaction in mitochondria. Mutations of IDH2 are more common than IDH1 mutations, 8 to 19% compared to 7 to 14% respectively,[5] in those affected with AML. Enasidenib disrupts this cycle by decreasing total (R)-2-HG levels in the mitochondria.

    History

    The U.S. Food and Drug Administration (FDA) granted the application for enasidenib fast track designation and orphan drug designation for acute myeloid leukemia in 2014.[6]

    Enasidenib was approved by the FDA in August 2017, for relapsed or refractory acute myeloid leukemia (AML) in people with specific mutations of the IDH2 gene, determined by an FDA-approved IDH2 companion diagnostic test.[5][7][8] The FDA considers it to be a first-in-class medication.[9]

    References

    1. 1 2 3 4 5 "Enasidenib Monograph for Professionals". Drugs.com. Archived from the original on 19 January 2021. Retrieved 15 December 2021.
    2. 1 2 3 4 5 6 7 "DailyMed - IDHIFA- enasidenib mesylate tablet, film coated". dailymed.nlm.nih.gov. Archived from the original on 23 March 2021. Retrieved 15 December 2021.
    3. 1 2 "Idhifa: Withdrawal of the marketing authorisation application". Archived from the original on 20 November 2021. Retrieved 15 December 2021.
    4. ↑ "Idhifa Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 16 April 2021. Retrieved 15 December 2021.
    5. 1 2 3 Kim ES (October 2017). "Enasidenib: First Global Approval". Drugs. 77 (15): 1705–1711. doi:10.1007/s40265-017-0813-2. PMID 28879540. S2CID 7685848.
    6. 1 2 Brunton LL, Hilal-Dandan R, Knollmann BC (eds.). Goodman & Gilman's the pharmacological basis of therapeutics (13th ed.). New York. ISBN 9781259584732. OCLC 993810322.
    7. ↑ "FDA Approves New Treatment for Leukemia". GEN. August 2, 2017. Archived from the original on November 7, 2017. Retrieved July 1, 2021.
    8. ↑ "Press release: FDA granted regular approval to enasidenib for the treatment of relapsed or refractory AML". FDA. August 1, 2017. Archived from the original on April 23, 2019. Retrieved July 1, 2021.
    9. ↑ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Archived from the original on 23 October 2020. Retrieved 16 September 2020.
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