Vorasidenib Explained
| Tradename: | Voranigo |
| Dailymedid: | Vorasidenib |
| Routes Of Administration: | By mouth |
| Atc Prefix: | None |
| Legal Us: | Rx-only |
| Legal Us Comment: | [1] |
| Cas Number: | 1644545-52-7 |
| Pubchem: | 117817422 |
| Iuphar Ligand: | 10663 |
| Drugbank: | DB17097 |
| Chemspiderid: | 64835242 |
| Unii: | 789Q85GA8P |
| Kegg: | D11834 |
| Chembl: | 4279047 |
| Iupac Name: | 6-(6-Chloropyridin-2-yl)-2-N,4-N-bis[(2''R'')-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine |
| C: | 14 |
| H: | 13 |
| Cl: | 1 |
| F: | 6 |
| N: | 6 |
| Stdinchi: | 1S/C14H13ClF6N6/c1-6(13(16,17)18)22-11-25-10(8-4-3-5-9(15)24-8)26-12(27-11)23-7(2)14(19,20)21/h3-7H,1-2H3,(H2,22,23,25,26,27)/t6-,7-/m1/s1 |
| Stdinchikey: | QCZAWDGAVJMPTA-RNFRBKRXSA-N |
| Smiles: | C[C@H](C(F)(F)F)NC1=NC(=NC(=N1)C2=NC(=CC=C2)Cl)N[C@H](C)C(F)(F)F |
Vorasidenib, sold under the brand name Voranigo, is an anti-cancer medication used for the treatment of certain forms of glioma. Vorasidenib acts to inhibit the enzymes isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2).
The most common adverse reactions include fatigue, headache, increased risk of COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizures.
Vorasidenib was approved for medical use in the United States in August 2024.[2] [3] It is the first approval by the US Food and Drug Administration (FDA) of a systemic therapy for people with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation.
Medical uses
Vorasidenib is indicated for the treatment of people aged twelve years of age and older with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation, following surgery including biopsy, sub-total resection, or gross total resection.
Side effects
The most common adverse reactions include fatigue, headache, increased risk of COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizures. The most common grade 3 or 4 laboratory abnormalities include increased alanine aminotransferase, increased aspartate aminotransferase, GGT increased, and decreased neutrophils.
History
Efficacy was evaluated in 331 participants with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation following surgery enrolled in INDIGO (NCT04164901), a randomized, multicenter, double-blind, placebo-controlled trial. Participants were randomized 1:1 to receive vorasidenib 40 mg orally once daily or placebo orally once daily until disease progression or unacceptable toxicity. Isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test. Participants randomized to placebo were allowed to cross over to vorasidenib after documented radiographic disease progression. Participants who received prior anti-cancer treatment, including chemotherapy or radiation therapy, were excluded.
Society and culture
Legal status
Vorasidenib was approved for medical use in the United States in August 2024.
The FDA granted the application for vorasidenib priority review, fast track, breakthrough therapy, and orphan drug designations.
Further reading
- Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, Peters KB, Ellingson BM, Rosenblum MK, Chun S, Le K, Tassinari A, Choe S, Toubouti Y, Schoenfeld S, Pandya SS, Hassan I, Steelman L, Clarke JL, Cloughesy TF . Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial . Nature Medicine . 29 . 3 . 615–622 . March 2023 . 36823302 . 10313524 . 10.1038/s41591-022-02141-2 .
- Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY . Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial . Clinical Cancer Research : An Official Journal of the American Association for Cancer Research . 27 . 16 . 4491–4499 . August 2021 . 34078652 . 8364866 . 10.1158/1078-0432.CCR-21-0611 .
- Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry JR, Giglio P, de la Fuente M, Maher EA, Schoenfeld S, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Cloughesy TF . Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma . The New England Journal of Medicine . 389 . 7 . 589–601 . August 2023 . 37272516 . 10.1056/NEJMoa2304194 .
- Popovici-Muller J, Lemieux RM, Artin E, Saunders JO, Salituro FG, Travins J, Cianchetta G, Cai Z, Zhou D, Cui D, Chen P, Straley K, Tobin E, Wang F, David MD, Penard-Lacronique V, Quivoron C, Saada V, de Botton S, Gross S, Dang L, Yang H, Utley L, Chen Y, Kim H, Jin S, Gu Z, Yao G, Luo Z, Lv X, Fang C, Yan L, Olaharski A, Silverman L, Biller S, Su SM, Yen K . Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers . ACS Medicinal Chemistry Letters . 9 . 4 . 300–305 . April 2018 . 29670690 . 5900343 . 10.1021/acsmedchemlett.7b00421 .
Notes and References
- Web site: Voranigo- vorasidenib citrate tablet, film coated . DailyMed . 9 August 2024 . 15 August 2024.
- Web site: FDA approves vorasidenib for Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation . U.S. Food and Drug Administration (FDA) . 6 August 2024 . 7 August 2024 . 7 August 2024 . https://web.archive.org/web/20240807035511/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation . live .
- Servier's Voranigo (vorasidenib) Tablets Receives FDA Approval as First Targeted Therapy for Grade 2 IDH-mutant Glioma . Servier Pharmaceuticals . PR Newswire . 6 August 2024 . 7 August 2024 . 7 August 2024 . https://web.archive.org/web/20240807072643/https://www.prnewswire.com/news-releases/serviers-voranigo-vorasidenib-tablets-receives-fda-approval-as-first-targeted-therapy-for-grade-2-idh-mutant-glioma-302215991.html . live .
