Voranigo
(Vorasidenib)Dosage & Administration
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Voranigo Prescribing Information
Indications and Usage (VORANIGO is indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection [see Dosage and Administration (2.1), Clinical Pharmacology (12.1)and Clinical Studies (14)] .VORANIGO is an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection. | 04/2025 |
Dosage and Administration, Patient Selection (Select patients with Grade 2 astrocytoma or oligodendroglioma for treatment with VORANIGO based on the presence of IDH1 or IDH2 mutations in tumor specimens [see Clinical Studies (14)] .Information on FDA-approved tests for detection of IDH1 or IDH2 mutations in Grade 2 astrocytoma or oligodendroglioma for selecting patients for treatment with VORANIGO is available at: https://www.fda.gov/CompanionDiagnostics. | 04/2025 |
Before initiating VORANIGO, evaluate blood chemistry and liver laboratory tests
Vorasidenib is a small molecule inhibitor that targets isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) enzymes. In vitro, vorasidenib inhibited the IDH1 wild type and mutant variants, including R132H and the IDH2 wild type and mutant variants. In cell-based and in vivo tumor models expressing IDH1 or IDH2 mutated proteins, vorasidenib decreased production of 2-hydroxyglutarate (2-HG) and partially restored cellular differentiation.
The efficacy of VORANIGO was evaluated in the INDIGO trial (Study AG881-C-004), a randomized, multicenter, double-blind, placebo-controlled study of 331 patients (NCT04164901). Eligible patients were required to have IDH1- or IDH2-mutant Grade 2 astrocytoma or oligodendroglioma with prior surgery including biopsy, sub-total resection, or gross total resection. Patients were required to have measurable, non-enhancing disease; patients with centrally confirmed minimal, non-nodular, non-measurable enhancement were eligible. Patients who received prior anti-cancer treatment, including chemotherapy or radiation therapy were excluded. Patients were randomized to receive either VORANIGO 40 mg orally once daily or placebo orally once daily until disease progression or unacceptable toxicity. IDH1 or IDH2 mutation status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test.
Randomization was stratified by local 1p19q status (co-deleted or not co-deleted) and baseline tumor size (diameter ≥2 cm or <2 cm). Patients who were randomized to placebo were allowed to cross over to receive VORANIGO after documented radiographic disease progression. Tumor assessments were performed every 12 weeks.
A total of 331 patients were randomized, 168 to the VORANIGO arm and 163 to the placebo arm. The median age was 40 years (range: 16 to 71); 57% were male; 78% were White, 4% were Asian, 1% were Black or African American and 16% had race not reported; 78% were not Hispanic or Latino; 52% oligodendroglioma and 48% astrocytoma; 79% had one prior surgery and 21% had ≥2 prior surgeries. In the VORANIGO arm, 14% of patients had biopsy, 48% had sub-total resection and 51% had gross-total resection. The majority of IDH1 mutations consisted of R132H (87%). The other alleles were reported as follows: R132C (5%), R132G (3%), R132L (1%), and R132S (1%). IDH2 mutations consisted of R172K (2%) and R172G (1%).
The major efficacy outcome was progression-free survival (PFS) as evaluated by a blinded independent review committee (BIRC) per modified Response Assessment in Neuro-Oncology for Low Grade Glioma (RANO-LGG) criteria.
Efficacy results are summarized in Table 7 and Figure 1.
| Efficacy Parameter | VORANIGO 40 mg daily (n=168) | Placebo (n=163) |
|---|---|---|
| CI = Confidence Interval | ||
Progression-Free Survival (PFS) | ||
Number of Events, n (%) | ||
| Progressive disease | 47 (28) | 88 (54) |
| Death | 0 | 0 |
Hazard ratio (95% CI) Stratified Cox proportional hazard model, stratified by 1p19q status and baseline tumor size. | 0.39 (0.27, 0.56) | |
p-value Based on one-sided stratified log-rank test compared to the pre-specified α of 0.000359 (one-sided). | <0.0001 | |
The major efficacy analyses are supported by a prospectively defined key secondary outcome measure time to next intervention (defined as the time from randomization to the initiation of first subsequent anticancer therapy or death due to any cause). The median time to next intervention was not reached for patients in the VORANIGO arm and 17.8 months for patients in the placebo arm (HR=0.26; 95% CI: [0.15, 0.43], p <0.0001).
- Recommended dosage in adults: ()
2.3 Recommended Dosage and AdministrationRecommended DosageAdult PatientsThe recommended dosage of VORANIGO in adult patients is 40 mg orally once daily until disease progression or unacceptable toxicity.
Pediatric Patients 12 Years and OlderThe recommended dosage of VORANIGO in pediatric patients 12 years and older is based on body weight:
- Patients weighing ≥40 kg: 40 mg orally once daily
- Patients weighing <40 kg: 20 mg orally once daily
Continue treatment with VORANIGO until disease progression or unacceptable toxicity.
AdministrationSwallow VORANIGO tablets whole with water with or without food
[see Clinical Pharmacology (12.3)]. Do not split, crush or chew tablets.Missed DoseTake VORANIGO tablets at about the same time each day. If a dose is missed, take the missed dose as soon as possible within 6 hours. If a dose is missed by more than 6 hours, skip the missed dose and take the next dose at the scheduled time.
VomitingIf vomiting occurs after taking a dose, do not take a replacement dose, and take the next dose at the scheduled time on the following day.
- 40 mg orally once daily
- Recommended dosage in pediatric patients 12 years of age and older based on body weight: ()
2.3 Recommended Dosage and AdministrationRecommended DosageAdult PatientsThe recommended dosage of VORANIGO in adult patients is 40 mg orally once daily until disease progression or unacceptable toxicity.
Pediatric Patients 12 Years and OlderThe recommended dosage of VORANIGO in pediatric patients 12 years and older is based on body weight:
- Patients weighing ≥40 kg: 40 mg orally once daily
- Patients weighing <40 kg: 20 mg orally once daily
Continue treatment with VORANIGO until disease progression or unacceptable toxicity.
AdministrationSwallow VORANIGO tablets whole with water with or without food
[see Clinical Pharmacology (12.3)]. Do not split, crush or chew tablets.Missed DoseTake VORANIGO tablets at about the same time each day. If a dose is missed, take the missed dose as soon as possible within 6 hours. If a dose is missed by more than 6 hours, skip the missed dose and take the next dose at the scheduled time.
VomitingIf vomiting occurs after taking a dose, do not take a replacement dose, and take the next dose at the scheduled time on the following day.
- ≥40 kg: 40 mg orally once daily
- <40 kg: 20 mg orally once daily
- Take with or without food. ()
2.3 Recommended Dosage and AdministrationRecommended DosageAdult PatientsThe recommended dosage of VORANIGO in adult patients is 40 mg orally once daily until disease progression or unacceptable toxicity.
Pediatric Patients 12 Years and OlderThe recommended dosage of VORANIGO in pediatric patients 12 years and older is based on body weight:
- Patients weighing ≥40 kg: 40 mg orally once daily
- Patients weighing <40 kg: 20 mg orally once daily
Continue treatment with VORANIGO until disease progression or unacceptable toxicity.
AdministrationSwallow VORANIGO tablets whole with water with or without food
[see Clinical Pharmacology (12.3)]. Do not split, crush or chew tablets.Missed DoseTake VORANIGO tablets at about the same time each day. If a dose is missed, take the missed dose as soon as possible within 6 hours. If a dose is missed by more than 6 hours, skip the missed dose and take the next dose at the scheduled time.
VomitingIf vomiting occurs after taking a dose, do not take a replacement dose, and take the next dose at the scheduled time on the following day.
Tablets:
- 10 mg: White to off-white, round film-coated tablet imprinted with "10" in black ink on one side and plain on the other side. Each tablet contains 10 mg of vorasidenib.
- 40 mg: White to off-white, oblong film-coated tablet imprinted with "40" in black ink on one side and plain on the other side. Each tablet contains 40 mg of vorasidenib.
- Lactation: Advise not to breastfeed. ()
8.2 LactationRisk SummaryThere are no data on the presence of vorasidenib or its metabolites in human milk, their effects on the breastfed child, or on milk production. Because of the potential for adverse reactions in breastfed children from VORANIGO, advise women not to breastfeed during treatment with VORANIGO and for 2 months after the last dose.
- Infertility: May impair fertility in males and females. ()
8.3 Females and Males of Reproductive PotentialBased on animal embryo-fetal toxicity studies, VORANIGO can cause fetal harm when administered to pregnant women
[see Use in Specific Populations (8.1)].Pregnancy TestingVerify pregnancy status in females of reproductive potential prior to starting VORANIGO
[see Use in Specific Populations (8.1)].ContraceptionFemalesAdvise females of reproductive potential to use effective nonhormonal contraception during treatment with VORANIGO and for 3 months after the last dose. VORANIGO can render some hormonal contraceptives ineffective
[see Drug Interactions (7.2)].MalesAdvise male patients with female partners of reproductive potential to use effective contraception during treatment with VORANIGO and for 3 months after the last dose.
InfertilityBased on findings in animals, VORANIGO may impair fertility in females and males of reproductive potential. The effects on female and male fertility were not reversible in rats
[see Nonclinical Toxicology (13.1)].
None.