New FDA Approval: VORANIGO® (vorasidenib)
The U.S Food and Drug Administration (FDA) recently approved VORANIGO® (vorasidenib), a prescription medicine used to treat adults and children 12 years of age and older with certain types of brain tumors called astrocytoma or oligodendroglioma with an isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, following surgery.
Read InpharmD's summary below:
| Drug Name |
VORANIGO® (vorasidenib) |
| Active Ingredient |
vorasidenib |
| Date of Approval |
August 6, 2024 |
| Manufacturer |
Servier Pharmaceuticals |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: VORANIGO® is FDA-approved for use in patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with susceptible isocitrate dehydrogenase-1(IDH1) or isocitrate dehydrogenase-2 (IDH2) mutations. It is used after surgery, including biopsy, sub-total resection, or gross total resection. |
| Therapeutic Class |
IDH1 and IDH2 inhibitors; Glioma Treatment |
| Formulation |
Tablets: 10 mg and 40 mg. |
| MoA |
VORANIGO®'s mechanism of action is by blocking IDH1 and IDH2 enzymes this decreases the production of 2-hydroxyglutarate (2-HG) and partially restores cellular differentiation to have its clinical effect. |
| Dosing and Administration |
Dosage Recommendations:
Adults: 40 mg orally once daily.
Pediatric Patients (12+ years):
≥ 40 kg: 40 mg orally once daily.
< 40 kg: 20 mg orally once daily.
The medication can be taken with or without food. |
| Administered by self or by HCP |
Administered by Self |
| Place in Therapy |
VORANIGO® marks a significant treatment advance in low-grade brain cancer, representing the first approval of a systemic therapy for grade 2 IDH-mutant brain cancers, such as oligodendrogliomas and astrocytomas, in over two decades. Prior to VORANIGO®, Servier's IDH1 inhibitor Tibsovo and IDH2 inhibitor Idhifa were used off-label due to limited treatment options but were not approved for brain cancer. VORANIGO®is specifically designed to penetrate the blood-brain barrier, enhancing its effectiveness against brain tumors.
VORANIGO® can cause serious side effects, including hepatotoxicity and embryo-fetal toxicity, and is not recommended while breastfeeding. Common adverse reactions (≥15%) include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. Avoid using VORANIGO® with strong and moderate CYP1A2 inhibitors, moderate CYP1A2 inducers, smoking tobacco, and CYP3A substrates, as these may reduce efficacy. If these interactions cannot be avoided, use non-hormonal contraception. |
| Expected Market Launch Date |
Already on Market |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
$39,881 a month |
| Product Discontinuation |
N/A |
| Clinical Trials |
In a double-blind, phase 3 trial, patients were randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles. The primary end point was imaging-based progression-free survival according to blinded assessment by an independent review committee. The key secondary end point was the time to the next anticancer intervention. Crossover to vorasidenib from placebo was permitted on confirmation of imaging-based disease progression. Safety was also assessed.
A total of 331 patients were assigned to receive vorasidenib (168 patients) or placebo (163 patients). At a median follow-up of 14.2 months, 226 patients (68.3%) were continuing to receive vorasidenib or placebo. Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.1 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.27 to 0.56; P<0.001). The time to the next intervention was significantly improved in the vorasidenib group as compared with the placebo group (hazard ratio, 0.26; 95% CI, 0.15 to 0.43; P<0.001). Adverse events of grade 3 or higher occurred in 22.8% of the patients who received vorasidenib and in 13.5% of those who received placebo. An increased alanine aminotransferase level of grade 3 or higher occurred in 9.6% of the patients who received vorasidenib and in no patients who received placebo.
In patients with grade 2 IDH-mutant glioma, vorasidenib significantly improved progression-free survival and delayed the time to the next intervention. |
| Sources |
U.S. Food and Drug Administration. FDA approves Vorasidenib for Grade 2 astrocytoma or oligodendroglioma with susceptible IDH1 or IDH2 mutation. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation
Drugs.com. FDA approves Voranigo (Vorasidenib) for Grade 2 IDH-mutant glioma. Available from: https://www.drugs.com/newdrugs/fda-approves-voranigo-vorasidenib-grade-2-idh-mutant-glioma-6342.html
PR Newswire. Servier’s Voranigo (Vorasidenib) tablets receive FDA approval as first targeted therapy for Grade 2 IDH-mutant glioma. Available from: 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
Servier Pharmaceuticals. Voranigo (Vorasidenib) for Grade 2 IDH-mutant glioma. Available from: https://d11vmvycldsjdg.cloudfront.net/7fffe4c3-9746-4e82-9582-df9879a712d5/5939acdd-1c44-41f5-b2f6-260ab3860288/5939acdd-1c44-41f5-b2f6-260ab3860288_web_ready__c.pdf
MedPage Today. FDA approves Servier’s Vorasidenib for Grade 2 IDH-mutant glioma. Available from: https://medcitynews.com/2024/08/brain-cancer-glioma-fda-approval-servier-pharmaceuticals-vorasidenib-voranigo/
Pharmaceutical Executive. FDA approves Servier's Voranigo for Grade 2 IDH-mutant glioma. Available from: https://www.pharmexec.com/view/fda-approves-servier-voranigo-grade-2-idh-mutant-glioma |
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