About VORANIGO (vorasidenib)
How do IDH1 and IDH2 mutations impact glioma?1
In patients with astrocytoma or oligodendroglioma, IDH1 and IDH2 mutations lead to the overproduction of 2-HG, an enzyme that disrupts normal cellular processes and contributes to impaired cellular differentiation and subsequent oncogenesis.
Read more about IDH1/2 mutations in glioma
2-HG, 2-hydroxyglutarate; IDH, isocitrate dehydrogenase.
How does VORANIGO work?1,2
VORANIGO inhibits mutated IDH1/2 enzymes in mIDH astrocytoma or oligodendroglioma, preventing the abnormal production of 2‑HG, a key driver of oncogenesis.
Read more about how VORANIGO works
2-HG, 2-hydroxyglutarate; IDH, isocitrate dehydrogenase.
Patients appropriate for VORANIGO
Is my patient appropriate for VORANIGO?2
VORANIGO is approved for the treatment of adult and pediatric patients who are ≥12 years of age with Grade 2 mIDH1/2 astrocytoma or oligodendroglioma, as detected by an FDA-approved test, following surgery, including biopsy, sub-total resection, or gross total resection.
Read more about patients who may be appropriate for treatment with VORANIGO
mIDH1/2, mutant isocitrate dehydrogenase-1 or mutant isocitrate dehydrogenase-2.
Does the National Comprehensive Cancer Network® (NCCN®) include vorasidenib (VORANIGO) in its guidance for treating Grade 2 glioma?3
Yes, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend vorasidenib (VORANIGO) for Grade 2 mIDH1/2 astrocytoma and oligodendroglioma for patients with a KPS ≥60.a
In the adjuvant setting:
- A preferred treatment option in patients without residual/measurable diseaseb
- An NCCN Category 1 preferred treatment option in patients with residual/measurable or recurrent disease, when up-front treatment with radiation therapy and chemotherapy is not preferred.
In the recurrent/progressive setting after radiation therapy and chemotherapy:
- A preferred treatment optionc
Read more about patients who may be appropriate for treatment with VORANIGO
aIf an IDH inhibitor is being considered for a patient with newly diagnosed oligodendroglioma or astrocytoma, the NCCN Panel strongly recommends multidisciplinary discussion or referral to a brain tumor center for consultation.
bNewly diagnosed patients with oligodendroglioma/astrocytoma who did not have residual disease were excluded from participation in the INDIGO study. Therefore it is unknown if this subset of patients would benefit from immediate treatment with an IDH inhibitor. The safety of long-term treatment with IDH inhibitors is unknown. NCCN recommends discussing the possible risks and benefits of starting treatment right away with an IDH inhibitor with these patients.
cFor recurrent disease, there are multiple reasonable options, but there is no uniformly recommended option at this time.
KPS, Karnofsky Performance Status; mIDH1/2, mutant isocitrate dehydrogenase-1 or mutant isocitrate dehydrogenase-2.
Can I use VORANIGO in my patients following gross total resection?2,4
Yes. In the VORANIGO arm of the INDIGO trial, 14% of patients had biopsy, 48% had sub-total resection, and 51% had gross total resection. VORANIGO is 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.
Read more about patients who may be appropriate for treatment with VORANIGO
IDH1 or IDH2, isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2.
Can I use VORANIGO in my patients that previously received chemotherapy and/or radiotherapy?2
Yes. There is not an exclusion for patients who received prior therapy. VORANIGO is 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.
Read more about patients who may be appropriate for treatment with VORANIGO
IDH1 or IDH2, isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2.
When after surgery is it appropriate to start treatment with VORANIGO in my patients?2
VORANIGO is appropriate for treatment initiation as soon as immediately after surgery and does not require any waiting period. VORANIGO is 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.
Read more about patients who may be appropriate for treatment with VORANIGO
IDH1 or IDH2, isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2.
Does disease progression or stability affect when I can start treatment with VORANIGO for my patients?2
There is no prespecified consideration relative to disease progression or stability for treatment with VORANIGO. VORANIGO is 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.
Read more about patients who may be appropriate for treatment with VORANIGO
IDH1 or IDH2, isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2.
VORANIGO efficacy
What kind of trial was INDIGO?2,5
INDIGO was a phase 3, randomized, multicenter, double-blind, placebo-controlled trial that evaluated the safety and efficacy of VORANIGO versus placebo in 331 patients with Grade 2 mIDH1/2 astrocytoma or oligodendroglioma. Patients had prior surgery including biopsy, sub-total resection, or gross total resection.
Read more about the INDIGO trial design
mIDH1 or mIDH2, mutant isocitrate dehydrogenase-1 or mutant isocitrate dehydrogenase-2.
Are there data beyond the primary analysis from INDIGO?6
Yes. Data from an extended analysis beyond the primary data were presented at the 2024 Society for Neuro-Oncology (SNO) conference and included 6 more months of additional data to the date of unblinding on March 7, 2023. The median follow-up was 19.8 months with VORANIGO, and 20.2 months with placebo.
What was the major efficacy outcome for VORANIGO in the INDIGO trial?2
The major efficacy outcome for VORANIGO was progression-free survival (PFS). In the primary analysis, VORANIGO significantly extended PFS, demonstrating a 61% reduced risk of disease progression or death with VORANIGO vs placebo (HR=0.39; 95% CI, 0.27-0.56; P<0.0001).
What was the key secondary outcome for VORANIGO in the INDIGO trial?2,6
The key secondary outcome for VORANIGO was time to next intervention (TTNI). In the primary analysis, VORANIGO demonstrated a statistically significant improvement in TTNI when compared to placebo (HR=0.26; 95% CI, 0.15-0.43; P<0.0001). Median TTNI was not reached for VORANIGO vs 17.8 months with placebo.
In the extended analysis, median TTNI was not reached with VORANIGO vs 20.1 months with placebo (HR=0.25; 95% CI, 0.16-0.40).
Read more about VORANIGO TTNI results
HR, hazard ratio.
Did the INDIGO trial measure tumor growth rate (TGR)?5,6
Yes, TGR was a secondary outcome in the INDIGO trial. TGR was defined as the on-treatment percentage change in tumor volume every 6 months. In the extended analysis, TGR in the VORANIGO arm was -1.3% vs 14.4% in the placebo arm. The TGR endpoint has not been validated and the clinical significance of the changes observed is not known. This outcome was not controlled for multiplicity.
Did the INDIGO trial measure the on-treatment seizure rate?2,4,6
Yes, on-treatment seizure rate was an exploratory outcome in the INDIGO trial. Investigators reported seizure as an adverse event (AE) for all grades in 16% of patients treated with VORANIGO and 15% of patients treated with placebo. The number and severity of seizures were self-reported using a diary during each cycle.
The on-treatment seizure rate for VORANIGO was 64% lower compared to placebo in the subgroup of patients who experienced at least one seizure. (ratio of rates, 0.36; 95% CI, 0.14-0.89). A rigorous statistical conclusion cannot be made because seizure activity was an exploratory outcome, and the results should be interpreted with caution. This outcome was not controlled for multiplicity.
VORANIGO safety
What were the common adverse reactions to VORANIGO in the INDIGO trial?2,5
The safety of VORANIGO was evaluated in 330 patients with Grade 2 mIDH astrocytoma or oligodendroglioma in the INDIGO trial. The most common (≥15%) adverse reactions were fatigue (37%), COVID-19 (33%), musculoskeletal pain (26%), diarrhea (25%), and seizure (16%).
Review full safety information for VORANIGO
mIDH, mutant isocitrate dehydrogenase.
What are the warnings and precautions associated with VORANIGO?2
VORANIGO can cause hepatic transaminase elevations, which can lead to hepatic failure, hepatic necrosis, and autoimmune hepatitis. Patients treated with VORANIGO experienced increased ALT and AST.
Based on findings from animal studies, VORANIGO can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Review the full warnings and precautions for VORANIGO
ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Does VORANIGO impact patients who are planning to become pregnant?2
VORANIGO may impair fertility in females and males of reproductive potential. Based on animal embryo-fetal toxicity studies, VORANIGO can cause fetal harm when administered to pregnant women.
Does VORANIGO render some hormonal contraceptives ineffective?2
Yes, VORANIGO can render some hormonal contraceptives ineffective.
What are the recommendations for using VORANIGO in patients who are pregnant or breastfeeding?2
Based on findings from animal studies and its mechanism of action, VORANIGO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus.
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.
Does VORANIGO have a boxed warning?
There is no boxed warning for VORANIGO. For more information on the warnings and precautions associated with treatment with VORANIGO, please refer to the Full Prescribing Information.
VORANIGO dosing
How is VORANIGO dosed?2
VORANIGO is dosed once daily. The recommended dosage of VORANIGO in adult patients is 40 mg orally once daily. In pediatric patients 12 years and older, the recommended dosage is based on body weight—40 mg orally once daily if weighing ≥40 kg or 20 mg orally once daily if weighing <40 kg. Continue treatment until disease progression or unacceptable toxicity.
What monitoring is required for VORANIGO?2
Monitor liver laboratory tests (AST, ALT, GGT, total bilirubin, and alkaline phosphatase) prior to the initiation of VORANIGO, every 2 weeks during the first 2 months of treatment, then monthly for the first 2 years of treatment, and as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue VORANIGO based on severity.
Review recommended dose modifications
ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase.
What caused discontinuation of VORANIGO in the INDIGO trial?2
Permanent discontinuation of VORANIGO due to an adverse reaction occurred in 3.6% of patients. Adverse reactions which resulted in permanent discontinuation of VORANIGO in ≥2% of patients included ALT increased (3%).
See more about VORANIGO dosing changes
ALT, alanine aminotransferase.
VORANIGO access and resources
Is there support for patients taking VORANIGO?
ServierONE offers helpful resources and tools to help your patients navigate treatment care, costs, and education throughout their journeys.
- Support with insurance coverage and reimbursement
- Financial assistance to help patients pay for their medication
- Prescription fulfillment through our network of specialty pharmacies and distributors
Visit ServierONE.com for more information about how ServierONE Patient Support Services can assist your patients
Is there financial support for patients taking VORANIGO?
The Commercial Copay Program can help with out-of-pocket costs:
Eligible patients may register online for the Commercial Copay Program at ServierOne-copay.com
How is VORANIGO distributed?
VORANIGO is available through specialty distributors that can ship directly to office- or hospital-based pharmacies, and specialty pharmacies that can ship VORANIGO to your patient’s home or preferred location.
How is VORANIGO supplied and stored?2
- VORANIGO is supplied in 40 mg or 10 mg tablets in 30-count bottles
- Store VORANIGO at 20 to 25 °C (68-77 °F) with permitted excursions between 15 to 30 °C (59-86°F).
1. Changing the mIDH Glioma Landscape
2. An important step forward in the treatment of mIDH glioma with VORANIGO
3. Diving into the data from the INDIGO trial
4. Extended analysis from the INDIGO trial: TGR and seizure data
5. Dosing and safety of VORANIGO
6. A new era in the treatment of Grade 2 mIDH glioma
7. Important Safety Information
