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Trade names | Voranigo |
AHFS/Drugs.com | Monograph |
MedlinePlus | a624055 |
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Routes of administration | By mouth |
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Chemical and physical data | |
Formula | C14H13ClF6N6 |
Molar mass | 414.74 g·mol−1 |
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Vorasidenib, sold under the brand name Voranigo, is an anti-cancer medication used for the treatment of certain forms of glioma. [5] [6] Vorasidenib is a dual mutant isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) inhibitor. [5] [6] In people with astrocytoma or oligodendroglioma, IDH1 and IDH2 mutations lead to overproduction of the oncogenic metabolite 2-hydroxyglutarate (2-HG), which results in impaired cellular differentiation contributing to oncogenesis. [7] By inhibiting the IDH1 and IDH2 mutated proteins, vorasidenib inhibits the abnormal production of 2-HG thereby leading to differentiation of malignant cells and a reduction in their proliferation. [7]
The most common adverse reactions include fatigue, headache, increased risk of COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizures. [6]
Vorasidenib was approved for medical use in the United States in August 2024. [6] [8] [9] 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. [6]
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. [6]
The most common adverse reactions include fatigue, headache, increased risk of COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizures. [6] The most common grade 3 or 4 laboratory abnormalities include increased alanine aminotransferase, increased aspartate aminotransferase, GGT increased, and decreased neutrophils. [6]
Agios Pharmaceuticals previously developed the mIDH1 inhibitor ivosidenib [10] and mIDH2 inhibitor enasidenib [11] [12] for treatment of acute myeloid leukemia (AML) with susceptible IDH1 or IDH2 mutations, respectively. However, ivosidenib and enasidenib have low brain exposure, precluding their use in gliomas. [13] Moreover, isoform switching between IDH1 and IDH2 has been observed as a mechanism of resistance to mIDH inhibitor therapy. [14] Vorasidenib was thus developed to improve blood-brain barrier penetration and inhibit both mIDH1/2. [13]
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. [6] Participants were randomized 1:1 to receive vorasidenib 40 mg orally once daily or placebo orally once daily until disease progression or unacceptable toxicity. [6] Isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test. [6] Participants randomized to placebo were allowed to cross over to vorasidenib after documented radiographic disease progression. [6] Participants who received prior anti-cancer treatment, including chemotherapy or radiation therapy, were excluded. [6]
Vorasidenib was approved for medical use in the United States in August 2024. [6] [15] The FDA granted the application for vorasidenib priority review, fast track, breakthrough therapy, and orphan drug designations. [6]
In July 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Voranigo, intended for the treatment of low grade astrocytoma or oligodendroglioma with an isocitrate dehydrogenase‑1 (IDH1) R132 or isocitrate dehydrogenase-2 (IDH2) R172 mutation in people aged twelve years of age and older weighing at least 40 kilograms (88 lb). [7] The applicant for this medicinal product is Les Laboratoires Servier. [7]